SNPMiner Trials by Shray Alag


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Report for Mutation D842V

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 18 clinical trials

Clinical Trials


1 Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene

This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.

NCT01243346 D842-related Mutant GIST Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene. --- D842V ---

To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). --- D842V ---

To determine the progression free survival rate at 6 months in patients with advanced GIST with the D842V mutation in the PDGFRA gene, when treated with CP-868,596 (crenolanib).. Obtain toxicity information. --- D842V ---

To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.. PKPD analysis. --- D842V ---

To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.. Inclusion Criteria - Male or female, of any racial or ethnic group - Age 18 years or older - Life expectancy of greater than 12 weeks - Patient able and willing to provide informed consent - Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN. - Total creatinine ≤ 1.5x ULN - ECOG Performance Status 0 - 2 (Appendix II) - Patients must have histologically or cytologically confirmed GIST with a D842-related mutation or deletion on the PDGFRA gene - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. --- D842V ---

In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST. --- D842V ---

In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST. --- D842V --- --- D842V ---

In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V. --- V561D --- --- D842V ---

In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V. --- V561D --- --- D842V --- --- T674I --- --- D842V ---

Primary Outcomes

Description: To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). Response will primarily be determined by RECIST criteria

Measure: The primary end-point is overall response rate

Time: 1.5 years

Secondary Outcomes

Description: To determine the progression free survival rate at 6 months in patients with advanced GIST with the D842V mutation in the PDGFRA gene, when treated with CP-868,596 (crenolanib).

Measure: Progression free survival rate

Time: 6 months

Description: To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.

Measure: Obtain toxicity information

Time: 1 year

Description: To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.

Measure: PKPD analysis

Time: 1 year

2 A Randomized Multicenter Phase III Trial Evaluating the Interest of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)

This is a 2 arms study concerning patients with primary GIST who followed an Imatinib adjuvant treatment for 3 years after surgery and who have a high risk of recurrence. In the first arm, patients will continue Imatinib treatment for 3 more years, allowing to determine if the continuation of this treatment is efficient for disease control, in terms of Disease Free Survival improvement. In the second arm, patients will discontinue the Imatinib treatment, as standard practice. This arm will allow to determine if the re-introduction of Imatinib at relapse is still an efficient treatment for the control of disease.

NCT02260505 Gastrointestinal Stromal Tumors Resected Gastrointestinal Stromal Tumors Non-metastatic High Risk of Recurrence KIT Gene Mutation Drug: Imatinib maintenance
MeSH: Gastrointestinal Stromal Tumors Recurrence Neoplasms
HPO: Gastrointestinal stroma tumor Neoplasm

Exclusion Criteria: - Pregnant or breastfeeding women - Patient concurrently using other approved or investigational antineoplastic agents - Any contra-indication to imatinib treatment as per Glivec® SPC - Patient with GIST harboring the mutation D842V in PDGFRA - Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results. --- D842V ---

Primary Outcomes

Description: Time from the date of randomisation to the first documented relapse or death due to any cause. Patients with no event at the time of analysis will be censored at the date of the last adequate tumour assessment. The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

Measure: Disease Free Survival (DFS)

Time: 6 years (i.e. at the the time of last patient last visit)

Secondary Outcomes

Description: Time from the date of randomization until the date of death due to any cause and censored at the date of last contact for patients alive at last contact. The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

Measure: Overall Survival (OS)

Time: 6 years (i.e. at the the time of last patient last visit)

Description: Time from the date of randomization until the date of first relapse under Imatinib treatment (i.e first relapse in the "Imatinib maintenance arm" and relapse after reintroduction of Imatinib in the "Interruption of Imatinib arm"). The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

Measure: Time to Secondary Resistance (TSR)

Time: 6 years (i.e. at the the time of last patient last visit)

Description: Percentage of patients in Complete Response (CR) after reintroduction of Imatinib treatment for patients assigned to the interruption arm and who experience GIST recurrence. CR is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Measure: Percentage of patients in Complete Response (%CR) in interruption arm after reintroduction of Imatinib

Time: 6 years (i.e. at the the time of last patient last visit)

Description: The assessment of safety will be based mainly on the frequency of AE based on the Common Toxicity Criteria version 4 grade. AE will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Patients with at least either one serious AE, or one grade 3-4, or one AE requiring the interruption of study treatment, will be described by study arm and compared using a Pearson's Chi2 test or a Fisher's exact test, if adequate. Patients will be analyzed according the duration of exposure to imatinib

Measure: Frequency of Adverse Events (AE)

Time: 6 years (i.e. at the the time of last patient last visit)

Description: QoL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire (QLQ-C30). Descriptive statistics (e.g. means and medians) will be used to summarize the scored scales at it scheduled assessment time point of the questionnaire. The distribution of time to definitive health-related QoL deterioration by study arms will be estimated using the Kaplan-Meier method. The time to definitive deterioration is defined as the time from the date of randomization to the date of event, wich is defined as > 10 points decrease from baseline of QLQ-C30 global score (items 29 and 30) or death due to any cause. If patient has not had an event, time to QoL deterioration will be censored at the date of last adequate evaluation.

Measure: Patient's Quality of Life (QoL)

Time: 6 years (i.e at the the time of last patient last visit)

3 Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)

This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

NCT02272998 Malignant Neoplasm Drug: ponatinib hydrochloride Other: laboratory biomarker analysis
MeSH: Neoplasms
HPO: Neoplasm

- Patients with known ponatinib-resistant gene alterations - PDGFRA D842V mutation - cKIT D816V mutation - FLT3 D835V/Y/H/F or Y842C mutations - FGFR3 K652E mutation - Major surgery (e.g. --- D842V ---

Primary Outcomes

Description: The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.

Measure: Overall response, defined as the number of patients who achieve any response according to disease type in the first 6 courses of treatment

Time: Up to 6 months

Secondary Outcomes

Description: Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

Measure: Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Time: Up to 30 days after last dose of study drug

Description: Collected and summarized by descriptive statistics. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.

Measure: Tolerability of the regimen, assessed by the number of patients who required dose modifications and/or dose delays

Time: Up to 30 days after last dose of study drug

Description: Kaplan-Meier curves will be used to estimate the survival distribution.

Measure: Overall survival

Time: The time from treatment initiation to death, assessed up to 52 weeks

Description: Kaplan-Meier curves will be used to estimate the survival distribution.

Measure: Progression free survival

Time: The time from treatment initiation to progression or death, assessed up to 52 weeks

Description: Calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for CBR will be calculated.

Measure: Clinical benefit rate (CBR)

Time: 6 months

Other Outcomes

Description: Correlative gene and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response vs. no response). Overall, hypothesis testing will largely be avoided given the sample size limitations.

Measure: Correlative gene and protein markers

Time: Up to 3 years (time of progression)

4 A Randomised Phase II Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST)

An open label randomised trial for adults with histologically confirmed measurable metastatic GIST who have received no other treatment for metastatic disease. The study aims to determine if an alternating regimen of imatinib and regorafenib has sufficient activity and safety in comparison to imatinib alone to warrant further evaluation as a first line treatment for metastatic GIST.

NCT02365441 Gastrointestinal Stromal Tumour Drug: Regorafenib Drug: imatinib
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

- The presence of PDGFR D842V mutation or other mutation known to cause imatinib resistance. --- D842V ---

Primary Outcomes

Description: PFS at 24 months as calculated from the time from either (i) randomization if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to the date of progression as determined by RECIST v1.1

Measure: Progression free survival at 24 months (disease progression or death)

Time: 24 Months

Secondary Outcomes

Description: Objective tumour response rate following 2 cycles of treatment

Measure: Objective tumour response rate at 16 weeks

Time: 16 weeks

Description: Clinical benefit rate (SD + PR + CR) following 2 cycles of treatment

Measure: Clinical benefit rate at 16 weeks

Time: 16 weeks

Description: complete response rate will be calculated by summing the number of participants assessed as having a complete response and dividing this by the total number of participants evaluable for response (according to RECIST Version 1.1).

Measure: Complete response rate

Time: 5 years

Description: Time to treatment failure is defined as the time from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.

Measure: Time to treatment failure

Time: 5 years

Description: Safety/toxicity/tolerability

Measure: Adverse Events

Time: 5 years

Description: Overall survival is defined as the interval from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to date of death from any cause, or the date of last known follow-up alive.

Measure: Overall survival

Time: 5 years

Other Outcomes

Description: This is defined as the rate of patients who proceed to surgery with the aim of resecting all remaining macroscopic disease.

Measure: Macroscopically complete removal of all residual disease by surgery

Time: 5 years

Description: to explore the relationship between change in PET imaging during washout period of regorafenib and imatinib (in subset of participants at selected centres)

Measure: Change in PET imaging during washout period of regorafenib and imatinib in those taking part in the PET substudy

Time: 3 years

Description: To explore the relationship between study endpoints and Imatinib plasma levels at 4 and 12 weeks after commencement of treatment in both arms. Arm B: Imatinib plasma levels at 3 and 11 weeks after commencement of treatment and regorafenib plasma levels 7 and 15 weeks after commencement of treatment.

Measure: Imatinib plasma levels 4 and 12 weeks after commencement of treatment in both arms. Arm B: Imatinib plasma levels at 3 and 11 weeks after commencement of treatment and regorafenib plasma levels 7 and 15 weeks after commencement of treatment.

Time: 3 years

Description: To explore the relationship between study endpoints and circulating other biomarkers as prognostic and/or predictive markers.

Measure: Change in circulating serum/plasma growth factor and cytokine levels over time(multiplex assay), Frequency of KIT/PDGFRA mutations in circulating blood DNA and DNA load as prognostic and/or predictive markers

Time: 3 years

Measure: Tumour tissue biomarkers including, but not limited to, proteins relating to EGFR and PDGFR signalling and angiogenesis.

Time: 3 years

Description: Rate of patients having macroscopically complete removal of all residual disease by surgery

Measure: Macroscopically complete removal of all residual disease by surgery

Time: 3 years

5 Three Versus Five Years of Adjuvant Imatinib as Treatment of Patients With Operable GIST With a High Risk for Recurrence: A Randomised Phase III Study

In this study, patients who have been diagnosed with gastrointestinal stromal tumor (GIST) and have been treated with adjuvant imatinib for 3 years after surgery will be randomly allocated in a 1:1 ratio to receive imatinib (Gleevec) for 2 more years (Arm A) or to stop imatinib (Arm B). The study participants are required to have histologically verified GIST with a high risk of GIST recurrence despite removal of all macroscopic GIST tissue at surgery and 3 years of adjuvant imatinib. The high risk of GIST recurrence is defined as one of the following: gastric GIST with mitotic count >10/50 high power fields (HPFs) of the microscope, non-gastric GIST with mitotic count >5/50 HPFs, or tumor rupture. Study participants allocated to Arm A will receive imatinib 400 mg/day for 24 months after the date of randomization. All study participants will be followed up using blood tests and computerized tomography (or MRI) of the abdomen. The computerized tomography examinations will be performed at 6 month intervals. A total of 300 patients will be entered to the study. The study hypothesis is that adjuvant imatinib given for a total of 5 years may prevent some of the GISTs to recur as compared to patients who receive adjuvant imatinib for 3 years, and there may be a difference in the rate of GIST recurrence between the two groups.

NCT02413736 Sarcoma Drug: Imatinib
MeSH: Sarcoma
HPO: Sarcoma Soft tissue sarcoma

- Presence of a substitution mutation at PDGFRA codon D842 (usually D842V). --- D842V ---

Primary Outcomes

Description: Time from the date of randomization to GIST recurrence or death.

Measure: Recurrence-free survival

Time: 5 years

Secondary Outcomes

Description: Time from the date of randomization to death.

Measure: Overall survival

Time: 5 years

Description: Time from the date of randomization to the date of death considered to be caused by GIST.

Measure: GIST-specific survival

Time: 5 years

Description: Adverse effects considered to be related to the treatment.

Measure: Adverse effects

Time: 5 years

6 A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (formerly BLU-285), administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

NCT02508532 Gastrointestinal Stromal Tumors (GIST) Other Relapsed or Refractory Sol Other Relapsed or Refractory Solid Tumors Drug: Avapritinib
MeSH: Gastrointestinal Stromal Tumors Neoplasms
HPO: Gastrointestinal stroma tumor Neoplasm

OR For Part 2: - Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα. --- D842V ---

- Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. --- D842V ---

Patients must not have a known D842V mutation in PDGFRα. --- D842V ---

Primary Outcomes

Measure: Part 1: Maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) of avapritinib

Time: During cycle 1 (28 days) of treatment for MTD and at the end of every cycle (28 days) for RP2D for approximately 24 months or earlier if patient terminates from the study

Measure: Parts 1 and 2: Number of patients with adverse and serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings

Time: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study

Description: Either complete response (CR) or partial response (PR)

Measure: Part 2: Overall response rate

Time: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter.

Secondary Outcomes

Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)

Measure: Maximum plasma concentration of avapritinib

Time: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)

Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)

Measure: Time to maximum plasma concentration of avapritinib

Time: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)

Description: CR, PR and stable disease (SD)

Measure: Duration of response

Time: Overall median and at 3, 6, and 12 months

Measure: Progression-free survival

Time: Overall median and at 3, 6, and 12 months

Description: Rate of CR, PR, and SD

Measure: Clinical benefit rate

Time: 16 weeks

Measure: Response rate as defined by Choi Criteria

Time: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter.

Measure: Median PFS on last prior anti-cancer therapy

Time: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter.

Measure: KIT, PDGFRα, and other cancer-relevant mutations present in tumor tissue at baseline and EOT

Time: Screening period (Day -31 to Day 0 before first dose) and at the end of treatment

Measure: Change from baseline in levels of KIT and PDGFRα mutant allele fractions in peripheral blood

Time: Baseline, Cycle 1 day 15, Cycle 2 and 3 day 1 and at End of treatment (at approximately 24 months or earlier if patient terminates from the study) and at the EOT

7 A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Malignancies

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase and an expansion phase.

NCT02571036 Gastrointestinal Stromal Tumors Advanced Systemic Mastocytosis Advanced Cancers Drug: DCC-2618 Drug: DCC-2618
MeSH: Gastrointestinal Stromal Tumors Mastocytosis Mastocytosis, Systemic
HPO: Gastrointestinal stroma tumor Mastocytosis

Patients with de novo imatinib resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are eligible without prior imatinib therapy. --- D816V --- --- D842V ---

Primary Outcomes

Description: Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

Measure: Safety/tolerability of oral DCC-2618: incidence of adverse events

Time: Approximately 24 months

Measure: Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose

Time: 18 months

Description: Objective response rate (ORR); Disease control rate (DCR)

Measure: Expansion Phase: Assess Antitumor Activity of DCC-2618 in all diseases

Time: Approximately 24 months

Secondary Outcomes

Measure: Determine the PK profile of oral DCC-2618

Time: Predose and up to 24 hours postdose (Cycle = 28 Days)

Description: Objective response rate (ORR); Disease control rate (DCR)

Measure: Escalation Phase: Assess Antitumor Activity of DCC-2618 in patients with advanced malignancies

Time: Approximately 24 months

8 Efficacy of Adjuvant Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index. Multicenter, Prospective, Randomized Study. Etude Multicentrique, Prospective, randomisée

Following the ACOSOG Z9001trial, imatinib received market authorization in Europe for patients with GIST at significant risk of relapse in the adjuvant setting, according to the classifications of Miettinen and Joensuu. Thereafter, the SSG XVIII / AI trial proved the need to revise the recommendations of the European Society for Medical Oncology regarding the optimal duration of treatment, which is currently three years. Patients at low risk of recurrence should not receive adjuvant treatment with imatinib and recommendations cannot be made from the literature data as to the indication of adjuvant treatment for patients with an intermediate risk of relapse. The provision of prognostic molecular markers in this group of so-called intermediate-risk subjects would facilitate the identification of responders to imatinib and avoid overtreating some patients and undertreating others who would benefit from Imatinib. Recently, Lagarde et al. have shown that the Genomic Index (GI = A ² / C, where A is the total number of alterations gains or losses and C is the number of chromosomes involved in these alterations in Comparative Genomic Hybridization array(CGH array)) could have prognostic value in GIST, particularly in intermediate risk GISTs. More recent work by the same author in 100 cases of GISTs with intermediate prognosis according to the classification of Miettinem identified two prognostic groups based on GI. The rate of metastatic relapse at 2 years was 30.6% in the group with GI greater than 10 versus 5.4% in the group with GI less than 10 (manuscript under preparation). Thus, it is legitimate to set up a randomized trial to study the effectiveness of adjuvant treatment with imatinib in the GIST population at intermediate risk of relapse and with a high GI. This study is a prospective randomized clinical trial: a phase III, open-label, 2 parallel groups, multicenter study. The primary objective of this study is to assess the efficacy of adjuvant Imatinib on rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index. The second objectives of this study are to compare the two therapeutic approaches in terms of metastasis-free survival at 1 year, 2 years and 3 years, overall survival, clinical and biological tolerance, safety and Quality of life of patients and caregivers. The eligible subjects must meet all of the following criteria : subject with a gastrointestinal stromal tumor, intermediary risk from the Armed Forces Institute of Pathology classification [Miettenen 2006], subject with Genomic Grade Index higher than 10 determined by CGH array, subject with surgery for primary tumor performed from 2 weeks to 2 months before starting adjuvant Imatinib mesylate, subject with no evidence of residual macroscopic disease after surgery and with a medical decision to prescribe imatinib. Subjects meeting any of the following criteria must not be enrolled : subject who have experienced spontaneous tumor rupture before surgery, subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor Block and subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor Block. The Standard Group will receive adjuvant imatinib at a dose of 400 mg per day for a period of 3 years. Patients will be assessed for metastases every three months for three years with thoraco-abdominal and pelvic CT scan. The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan. The estimated proportion of subjects relapsing at 2 years will be 30% in the experimental group and 2.5% in the standard group: alpha risk, 5%, power 80%. A total of 80 subjects (40 in each arm) will be included. This is a trial combining two learned societies that already are taking part in many clinical trials in France (French Sarcoma Group and French Digestive Cancer Federation). The expected benefits for patients are : not treat subjects for whom this treatment would offer too little benefit weighed against the disadvantages and treat subjects in whom this treatment would provide a real benefit and reduce the cost of treatment in patients who would not benefit from being treated by imatinib. The originality of this study is that it will include molecular data in the therapeutic decision and demonstrate the concept of individualized treatment in this patient population. This could ultimately change the current recommendations.

NCT02576080 Gastrointestinal Stromal Tumor Drug: Imatinib Other: Surveillance
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

Subjects meeting any of the following criteria must not be enrolled : subject who have experienced spontaneous tumor rupture before surgery, subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor Block and subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor Block. --- D842V ---

- Subject with a contraindication to Imatinib, a known hypersensitivity to the active substance or to any of the excipients (ambivalence clause); - Subject treated with medicinal products that induce CYP3A4; - Subject who have experienced spontaneous tumor rupture before surgery (risk of spread); - Subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor block; - Subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor block Inclusion Criteria: - Man or woman 18 years old or over and PS:0-2 - No prior radiation therapy, no prior chemotherapy, no molecular targeted or biological therapy - Subject with a gastrointestinal stromal tumor, intermediary risk from the Armed Forces Institute of Pathology classification [Miettenen 2006] - Subject with Genomic Grade Index higher than 10 determined by CGH array; - Subject with surgery for primary tumor performed from 2 weeks to 2 months before starting adjuvant Imatinib mesylate; - Subject with no evidence of residual macroscopic disease after surgery (RO). --- D842V ---

- Subject with a contraindication to Imatinib, a known hypersensitivity to the active substance or to any of the excipients (ambivalence clause); - Subject treated with medicinal products that induce CYP3A4; - Subject who have experienced spontaneous tumor rupture before surgery (risk of spread); - Subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor block; - Subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor block Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumors null --- D842V ---

Primary Outcomes

Description: The primary objective of this study is to assess the efficacy of adjuvant Imatinib on rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index.

Measure: Rate of metastatic relapse in GIST patient

Time: 5 years

Secondary Outcomes

Description: Median in month(s)

Measure: Overall survival

Time: 5 years

Description: Safety and tolerance will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) at 15 days, 1 month and every three months. The investigator will grade all adverse events and severe adverse events (defined by the standard medical dictionary for regulatory activities, MedDRA) according to the NCI-CTCAE (version 4.0). Adverse events will be grouped by system organ classes.

Measure: Clinical and biological tolerance

Time: 5 years

Description: French version of the SF36. European Organization for Research and Treatment of Cancer QLQ-C30

Measure: Patients' quality of life

Time: 5 years

9 A Phase 1, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CDX-0158 in Adult Patients With KIT Positive Advanced Solid Tumors.

This is a dose-escalation Phase 1 study designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose, and the safety profile of CDX-0158 in patients with KIT-positive advanced solid malignancies refractory to standard therapy or for which no standard therapy exists.

NCT02642016 Advanced Cancer Biological: CDX-0158 (formerly known as KTN-0158)

If documented to have SDH deficient or PDGFRA-D842V GIST, no prior therapy is required for study entry. --- D842V ---

Primary Outcomes

Measure: Dose limiting toxicities for CDX-0158

Time: Participants will be evaluated for DLTs from the first adminstration of CDX-0158 through 21 days following initial dosing.

10 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Crenolanib in Subjects With Advanced or Metastatic Gastrointestinal Stromal Tumors With a D842V Mutation in the PDGFRA Gene

This is a multicenter, randomized, double-blinded, placebo-controlled, trial of oral crenolanib versus oral placebo in combination with best supportive care in subjects with advanced or metastatic GIST with a D842V mutation in the PDGFRA gene. Approximately 120 subjects will be randomized in a 2:1 ratio to receive either crenolanib 100 mg or matching placebo orally (PO) 3 times daily (TID) in combination with best supportive care.

NCT02847429 GIST With D842V Mutated PDGFRA Gene Drug: Crenolanib Drug: Placebo

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Crenolanib in Subjects With Advanced or Metastatic Gastrointestinal Stromal Tumors With a D842V Mutation in the PDGFRA Gene. --- D842V ---

Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST This is a multicenter, randomized, double-blinded, placebo-controlled, trial of oral crenolanib versus oral placebo in combination with best supportive care in subjects with advanced or metastatic GIST with a D842V mutation in the PDGFRA gene. --- D842V ---

Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST This is a multicenter, randomized, double-blinded, placebo-controlled, trial of oral crenolanib versus oral placebo in combination with best supportive care in subjects with advanced or metastatic GIST with a D842V mutation in the PDGFRA gene. --- D842V --- --- D842V ---

Inclusion Criteria: 1. Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing 2. Measurable disease as per modified RECIST 1.1 • A lesion in an area that was previously treated with local therapy (e.g. --- D842V ---

chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents) or investigational device within 3 weeks or 5 half-lives (if the drug's half-life in subject is known) prior to randomization, whichever is shorter Inclusion Criteria: 1. Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing 2. Measurable disease as per modified RECIST 1.1 • A lesion in an area that was previously treated with local therapy (e.g. --- D842V ---

chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents) or investigational device within 3 weeks or 5 half-lives (if the drug's half-life in subject is known) prior to randomization, whichever is shorter GIST With D842V Mutated PDGFRA Gene null --- D842V ---

Primary Outcomes

Measure: Progression-free survival (PFS) will be measured from the date of randomization to the date of the first objective radiological disease progression according to centralized committee assessment using modified RECIST version 1.1 or death.

Time: 3 years

Secondary Outcomes

Measure: Overall survival (OS) will be measured from the date of randomization to the date of death from any cause. OS will be estimated using the Kaplan-Meier method.

Time: 3 years

11 A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of Oral HQP1351 in Patients With GIST or Other Solid Tumors.

This study is a Multi-center, Open-label Phase 1 Study to Determine the Recommend Phase 2 Dose (RP2D) and Evaluate PK/PD and preliminary Efficacy of HQP1351 in Patients With GIST or Other Solid Tumors.

NCT03594422 Gastrointestinal Stromal Tumor (GIST) Solid Tumor, Adult Drug: HQP1351
MeSH: Gastrointestinal Stromal Tumors Neoplasms
HPO: Gastrointestinal stroma tumor Neoplasm

Among them, GIST patients are required primary imatinib resistance (PDGFRA D842V mutation or NF1 mutation) or failed to previous treatment with imatinib or imatinib and at least one other TKI. 3. ECOG≤ 2. 4. Estimated survival at least 3 months. --- D842V ---

Primary Outcomes

Description: Patients with HQP1351 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.03.

Measure: Safety and tolerance

Time: 30 days after the last dose of HQP1351

Secondary Outcomes

Description: Pharmacokinetic evaluation

Measure: Maximum plasma concentration (Cmax) of HQP1351 on Day 1 and Day 27 post HQP1351 treatment on cycle 1.

Time: 28 days

Description: Pharmacokinetic evaluation

Measure: Area under the plasma concentration versus time curve (AUC) of HQP1351 on Day 1 and Day 27 post HQP1351 treatment on cycle 1.

Time: 28 days

Description: Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1

Measure: Anti-tumor activities of HQP1351

Time: 3-6 months

12 Compassionate Use of Crenolanib for Cancers With Platelet Derived Growth Factor Receptor Alpha (PDGFRa) Mutations, PDGFRa Amplifications or Fms-like Tyrosine Kinase 3 (FLT3) Mutations

Compassionate use of crenolanib for patients with serious life-threatening illness that have exhausted all available therapies used to treat the disease, with no other viable therapy options, who is not eligible for clinical trials. This program is designed to evaluate the requests on a patient by patient basis. Patients must have documented evidence of a point mutation in position 842 in platelet derived growth factor receptor alpha (PDGFRA-D842V) or amplification of PDGFRA or internal tandem duplication within the FMS-like tyrosine kinase 3 (FLT3-ITD) or point mutations within the tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD)

NCT03620318 FLT3-ITD Mutation FLT3/TKD Mutation PDGFR-Alpha D842V PDGFRA Gene Amplification Drug: Crenolanib besylate

Patients must have documented evidence of a point mutation in position 842 in platelet derived growth factor receptor alpha (PDGFRA-D842V) or amplification of PDGFRA or internal tandem duplication within the FMS-like tyrosine kinase 3 (FLT3-ITD) or point mutations within the tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD) Inclusion Criteria: - Subject must have a serious life threatening cancer with FLT3/PDGFRa mutation or PDGFRa amplification who has exhausted all other treatment options - Subject and their partner (if adults) must use 2 forms of contraception during study and for 3 months following last dose of study drug Exclusion Criteria: - Subject is eligible for enrollment in an ongoing clinical trial - Subject has any condition which, in the investigator's opinion makes the subject unsuitable for participation Inclusion Criteria: - Subject must have a serious life threatening cancer with FLT3/PDGFRa mutation or PDGFRa amplification who has exhausted all other treatment options - Subject and their partner (if adults) must use 2 forms of contraception during study and for 3 months following last dose of study drug Exclusion Criteria: - Subject is eligible for enrollment in an ongoing clinical trial - Subject has any condition which, in the investigator's opinion makes the subject unsuitable for participation FLT3-ITD Mutation FLT3/TKD Mutation PDGFR-Alpha D842V PDGFRA Gene Amplification This program is being offered on a patient by patient basis while phase 3 studies with crenolanib are ongoing. --- D842V ---

Patients must have documented evidence of a point mutation in position 842 in platelet derived growth factor receptor alpha (PDGFRA-D842V) or amplification of PDGFRA or internal tandem duplication within the FMS-like tyrosine kinase 3 (FLT3-ITD) or point mutations within the tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD) Inclusion Criteria: - Subject must have a serious life threatening cancer with FLT3/PDGFRa mutation or PDGFRa amplification who has exhausted all other treatment options - Subject and their partner (if adults) must use 2 forms of contraception during study and for 3 months following last dose of study drug Exclusion Criteria: - Subject is eligible for enrollment in an ongoing clinical trial - Subject has any condition which, in the investigator's opinion makes the subject unsuitable for participation Inclusion Criteria: - Subject must have a serious life threatening cancer with FLT3/PDGFRa mutation or PDGFRa amplification who has exhausted all other treatment options - Subject and their partner (if adults) must use 2 forms of contraception during study and for 3 months following last dose of study drug Exclusion Criteria: - Subject is eligible for enrollment in an ongoing clinical trial - Subject has any condition which, in the investigator's opinion makes the subject unsuitable for participation FLT3-ITD Mutation FLT3/TKD Mutation PDGFR-Alpha D842V PDGFRA Gene Amplification This program is being offered on a patient by patient basis while phase 3 studies with crenolanib are ongoing. --- D842V --- --- D842V ---


13 Early Access Program (EAP) for Avapritinib in Patients With Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)

This is a US, multicenter, open-label expanded access program to provide access to avapritinib until such time that avapritinib becomes available through other mechanisms or the Sponsor chooses to discontinue the program.

NCT03862885 GIST Drug: Avapritinib

4. Patient has received 3 or more TKI therapies including imatinib, or the patient has GIST that carries a mutation in exon 18 of the PDGFRA gene (such as D842V). 5. --- D842V ---


14 Efficacy and Safety of Anlotinib in Patients With Advanced Gastrointestinal Stromal Tumor After Failure of Imatinib: a Prospective, Single Arm and Multicenter Trial

Gastrointestinal stromal tumors (GIST) compose approximately 20% of soft tissue sarcomas with an annual incidence of approximately 7 per million population. GISTs occur throughout the GI tract, most commonly in the stomach or small intestine. The main treatment for localised GIST is surgical resection. At least 40% of these patients will develop recurrence or metastasis following complete resection. Local recurrence, liver metastases and/or dissemination within the abdominal cavity are the most common clinical manifestations. Although imatinib and sunitinib has greatly improved the quality of life and survival of patients with advanced GIST. Analysis of clinical trials revealed that patients with tumours with KIT exon 17 or 18 mutations, with a second mutation in KIT exon 17 or 18, had worse responses to imatinib and sunitinib. Some patients with PDGFRA D842V mutation do not respond to the present standard therapies. Anlotinib (1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-Yl] oxy] methyl]cyclopropanamine dihydrochloride) , a multi-targeted tyrosine kinase inhibitor (TKI), characterized as a highly selective and potent c-KIT, VEGFR, PDGFR, FGFR inhibitor. In vitro and in vivo, Anlotinib has a broad spectrum of inhibitory action on tumor angiogenesis and growth, which showed broad activity against soft tissue sarcoma and GIST with D842V, D816H, V560G and V654A mutations. In 2015, the US FDA granted orphan drug treatment for ovarian cancer.

NCT04106024 Gastrointestinal Stromal Tumors Drug: Anlotinib
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

Some patients with PDGFRA D842V mutation do not respond to the present standard therapies. --- D842V ---

In vitro and in vivo, Anlotinib has a broad spectrum of inhibitory action on tumor angiogenesis and growth, which showed broad activity against soft tissue sarcoma and GIST with D842V, D816H, V560G and V654A mutations. --- D842V ---

Primary Outcomes

Description: Progress Free Survival

Measure: PFS

Time: 18 month

15 A Multicentre, Comparative, Placebo-controlled, Double-blinded, Phase II Study of the Efficacy of Lenvatinib in Patients With Locally Advanced or Metastatic GIST After Failure of Imatinib and Sunitinib

The primary objective is to compare the efficacy of lenvatinib plus Best Supportive Care versus Placebo plus Best Supportive Care in the treatment of patients with advanced GIST, after failure of imatinib and sunitinib.

NCT04193553 Gastro Intestinal Stromal Tumour Drug: Lenvatinib Drug: Placebo Other: Best supportive care
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

Patient with a documented mutation in PDGFRA exon 18 (D842V substitution). --- D842V ---

Primary Outcomes

Description: PFS, defined as the time from the date of randomisation to the date of the first documented radiological progression (RECIST 1.1) or death due to any cause. PFS will be estimated using the Kaplan-Meier method and will be described in terms of median PFS per arm, and hazard ratio for progression between the 2 arms. Associated 2-sided 95% CI for the estimates will be provided.

Measure: Progression-Free Survival (PFS)

Time: Up to 30 months

Secondary Outcomes

Description: OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

Measure: Overall Survival (OS)

Time: Up to 30 months

Description: ORR, is the proportion of patients with a Complete Response or Partial Response as Best Overall Response.

Measure: Objective Response Rate (ORR) for patient in the blinded part of the study

Time: Up to 30 months

Description: BOR, is described as the proportion of patients with a best overall response of Complete Response, Partial Response, Stable Disease or Progressive Disease.

Measure: Best Overall Response (BOR) for patient in the blinded part of the study

Time: Up to 30 months

Description: QoL, will be assessed using the EORTC QLQ-C30. Scores will be calculated at each time point according to the scoring manuals. Descriptive statistics will be used to evaluate baseline scores and evolution of scores from baseline to each time point. Data will be compared between arms using the Student's t-test.

Measure: Quality of Life (QoL) for patient in the blinded part of the study

Time: Up to 30 months

Description: The safety will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Adverse events will be coded according to the MedDRA®.

Measure: Patient's tolerance to treatment

Time: Up to 30 months

Description: OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

Measure: Progression-Free Survival (PFS) In patients from the placebo arm who switched into the active treatment group

Time: Up to 30 months

Other Outcomes

Description: Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)

Measure: Mutation profile : KIT

Time: Inclusion

Description: Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)

Measure: Mutation profile: PDGFR

Time: Inclusion

16 A Phase I/II Clinical Study of Avapritinib in Chinese Subjects With Unresectable or Metastatic Gastrointestinal Stromal Tumor

This study is an open-label, multicenter, phase I/II study to evaluate the safety, PK and clinical efficacy of avapritinib in Chinese subjects with unresectable or metastatic GIST. The study consists of two parts: dose escalation (phase I) and dose expansion (phase II).

NCT04254939 Gastrointestinal Stromal Tumors Drug: CS3007 (BLU-285)
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

For phase I study, the subject must have histologically or cytologically confirmed unresectable or metastatic GIST that progressed after imatinib and at least one additional TKI treatment, or who cannot tolerate the standard treatment or have D842V mutation in the PDGFRα gene. --- D842V ---

2. For phase II study: i) Group 1: Chinese subjects with unresectable GIST harboring D842V mutation in PDGFRα gene. --- D842V ---

Patients must not have a known D842V mutation in PDGFRα gene. --- D842V ---

Primary Outcomes

Measure: Phase I: Recommended Phase II dose (RP2D), incidence of dose limiting toxicities (DLT) in Cycle 1, incidence and severity of adverse events and serious adverse events and changes in vital signs, clinical laboratory results and ECG findings

Time: at the end of Cycle 1 (each cycle is 28 days) for RP2D and DLT; during every cycle through 30 days after the last dose of study drug, an average of approximately 24 months, for other measures

Measure: Phase II: ORR based on mRESIST 1.1

Time: At Cycle 3 (each cycle is 28 days) Day 1, then every 2 cycles until Cycle 13, they every 3 cycles through study completion, disease progression or patient discontinuation from the study (whichever comes first), an average of approximately 24 months

17 A Phase II, Single Arm Study of Avelumab In Combination With Axitinib in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumor After Failure of Standard Therapy - AXAGIST

To assess anti-tumor activity of avelumab in combination with axitinib in patients with unresectable/metastatic GIST after progression on second or third line treatment (after failure on at least of imatinib and sunitinib) in terms of progression-free survival (PFS)

NCT04258956 Gastrointestinal Stromal Tumors Drug: Axitinib
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

- Patients with PDGFRA D842V mutations are not eligible for this study. --- D842V ---

Primary Outcomes

Measure: Participants Achieving 3-Month Progression-Free Survival (PFSR) Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria

Time: 12 weeks

18 Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Subjects With Advanced Gastrointestinal Stromal Tumor

This study will assess the safety, efficacy, and pharmacokinetics of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST).

NCT04276415 Gastrointestinal Stromal Tumors Drug: DS-6157a
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

Inclusion Criteria: - Written informed consent - At least 20 years old in Japan or 18 years old in other countries at the time of signature of the informed consent form (ICF), following local regulatory requirements - Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 - Has histopathologically documented unresectable and/or metastatic GIST meeting the criteria below: - Dose Escalation (Part 1): Participants should meet one of the following criteria: 1. (For US sites only) Participants with GIST who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment or who are not candidates for post-IM standard of care treatment 2. (For Japan sites only) Participants with GIST who have received all the existing standard of care treatments or who are not candidates for one or more available post-IM standard of care treatments 3. Participants with GIST who are not candidates for IM or curative intent surgical treatment (i.e., subjects without activating KIT or platelet-derived growth factor receptor alpha (PDGFRa) mutations, with PDGFRa D842V mutations, or are KIT negative by local results) - Dose Expansion (Part 2) Cohort 1: Participants with GIST who have progressed on or are intolerant to IM and at least one post-IM treatment - Dose Expansion (Part 2) Cohort 2: Participants with GIST who have progressed on IM and had not received a post-IM treatment (2nd line) - Consents to provide fresh tumor biopsy tissue samples both before and on DS-6157a treatment for the measurement of GPR20 levels by immunohistochemistry and other biomarkers - Has a left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 28 days before study treatment - Has at least 1 measurable lesion based on RECIST Version 1.1 as assessed by the Investigator - Has adequate organ function within 7 days before the start of study treatment, defined as: 1. Platelet count ≥100,000/mm^3 2. Hemoglobin ≥8.5 g/dL 3. Absolute neutrophil count ≥1,500/mm^3 4. Creatinine clearance ≥50 mL/min 5. Aspartate aminotransferase ≤3 × upper limit of normal (ULN) (if liver metastases are present, ≤5 × ULN) 6. Alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 × ULN) 7. Total bilirubin ≤1.5 × ULN or ≤3.0 × ULN for participants with documented history of Gilbert's Syndrome - Has an adequate treatment washout period prior to start of study treatment, defined as: 1. Major surgery: ≥4 weeks (or 2 weeks for minor surgeries) 2. Radiation therapy: ≥3 weeks (or 2 weeks for palliative radiation excluding pelvic radiation) 3. Systemic anti-cancer therapy (except for anti-androgen for prostate cancer and bisphosphonate, denosumab, or medroxyprogesterone acetate for bone metastases): - Cytotoxic chemotherapy: ≥3 weeks or 5 times the terminal elimination half-life (t½) of the chemotherapeutic agent, whichever is shorter - Antibody and antibody-conjugates therapy: ≥3 weeks or 5 times the t½, whichever is longer - Prior tyrosine kinase inhibitors (TKIs): washout period from 2 to 21 days depending on the TKI - Immunotherapy: ≥4 weeks. --- D842V ---

- Has evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as manifest by the detectable viral load (HBV-DNA or HCV-RNA, respectively) - Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days before study treatment - Women who plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment - Men who plan to father a child while in the study and for at least 4 months after the last administration of study treatment - Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, substance abuse, or other medical condition that would increase the risk of toxicity or interfere with participation of the participant or evaluation of the clinical study Inclusion Criteria: - Written informed consent - At least 20 years old in Japan or 18 years old in other countries at the time of signature of the informed consent form (ICF), following local regulatory requirements - Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 - Has histopathologically documented unresectable and/or metastatic GIST meeting the criteria below: - Dose Escalation (Part 1): Participants should meet one of the following criteria: 1. (For US sites only) Participants with GIST who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment or who are not candidates for post-IM standard of care treatment 2. (For Japan sites only) Participants with GIST who have received all the existing standard of care treatments or who are not candidates for one or more available post-IM standard of care treatments 3. Participants with GIST who are not candidates for IM or curative intent surgical treatment (i.e., subjects without activating KIT or platelet-derived growth factor receptor alpha (PDGFRa) mutations, with PDGFRa D842V mutations, or are KIT negative by local results) - Dose Expansion (Part 2) Cohort 1: Participants with GIST who have progressed on or are intolerant to IM and at least one post-IM treatment - Dose Expansion (Part 2) Cohort 2: Participants with GIST who have progressed on IM and had not received a post-IM treatment (2nd line) - Consents to provide fresh tumor biopsy tissue samples both before and on DS-6157a treatment for the measurement of GPR20 levels by immunohistochemistry and other biomarkers - Has a left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 28 days before study treatment - Has at least 1 measurable lesion based on RECIST Version 1.1 as assessed by the Investigator - Has adequate organ function within 7 days before the start of study treatment, defined as: 1. Platelet count ≥100,000/mm^3 2. Hemoglobin ≥8.5 g/dL 3. Absolute neutrophil count ≥1,500/mm^3 4. Creatinine clearance ≥50 mL/min 5. Aspartate aminotransferase ≤3 × upper limit of normal (ULN) (if liver metastases are present, ≤5 × ULN) 6. Alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 × ULN) 7. Total bilirubin ≤1.5 × ULN or ≤3.0 × ULN for participants with documented history of Gilbert's Syndrome - Has an adequate treatment washout period prior to start of study treatment, defined as: 1. Major surgery: ≥4 weeks (or 2 weeks for minor surgeries) 2. Radiation therapy: ≥3 weeks (or 2 weeks for palliative radiation excluding pelvic radiation) 3. Systemic anti-cancer therapy (except for anti-androgen for prostate cancer and bisphosphonate, denosumab, or medroxyprogesterone acetate for bone metastases): - Cytotoxic chemotherapy: ≥3 weeks or 5 times the terminal elimination half-life (t½) of the chemotherapeutic agent, whichever is shorter - Antibody and antibody-conjugates therapy: ≥3 weeks or 5 times the t½, whichever is longer - Prior tyrosine kinase inhibitors (TKIs): washout period from 2 to 21 days depending on the TKI - Immunotherapy: ≥4 weeks. --- D842V ---

Primary Outcomes

Measure: Number of participants with dose-limiting toxicities (DLT) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST)

Time: Baseline up to 5 years post-treatment

Measure: Summary of most frequently reported (≥10%) treatment-emergent adverse events (TEAEs) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST)

Time: Baseline up to 5 years post-treatment

Measure: Objective response rate (ORR) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST) (Dose expansion)

Time: Baseline up to 5 years post-treatment

Measure: Duration of response (DoR) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST) (Dose expansion)

Time: Baseline up to 5 years post-treatment

Measure: Disease control rate (DCR) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST) (Dose expansion)

Time: Baseline up to 5 years post-treatment

Measure: Progression-free survival (PFS) following intravenous administration of DS-6157a in patients with advanced gastrointestinal stromal tumors (GIST) (Dose expansion)

Time: Baseline up to 5 years post-treatment

Secondary Outcomes

Measure: Pharmacokinetic Analysis: Area under the plasma concentration-time curve up to the last quantifiable time (AUClast) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Pharmacokinetic Analysis: Area under the plasma concentration-time curve in the dosing interval (AUCtau) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Pharmacokinetic Analysis: Time to maximum plasma concentration (Tmax) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Pharmacokinetic Analysis: Maximum plasma concentration (Cmax) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Pharmacokinetic Analysis: Lowest concentration reached after a single dose (Ctrough) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Pharmacokinetic Analysis: Terminal elimination half-life (t1/2) for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a following intravenous administration of DS-6157a

Time: Post Cycle 1 and Cycle 3 doses (each cycle is 21 days)

Measure: Objective response rate (ORR) following intravenous administration of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST) (Dose escalation)

Time: Baseline up to 5 years post-treatment

Measure: Duration of response (DoR) following intravenous administration of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST) (Dose escalation)

Time: Baseline up to 5 years post-treatment

Measure: Disease control rate (DCR) following intravenous administration of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST) (Dose escalation)

Time: Baseline up to 5 years post-treatment

Measure: Progression-free survival (PFS) following intravenous administration of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST) (Dose escalation)

Time: Baseline up to 5 years post-treatment

Measure: Number of participants with anti-drug antibodies against DS-6157a following intravenous administration of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST)

Time: Baseline up to 5 years post-treatment


HPO Nodes


Gastrointestinal stroma tumor
Genes 25
PDGFRA CD19 SDHB KIT CD81 SDHC PRKCD SDHB TNFRSF13B TNFRSF13C MS4A1 NFKB1 KIT NFKB2 SDHA SDHC TNFSF12 SDHC CR2 ICOS TNFSF12 SDHB SDHB SDHD KIT
Neoplasm
Genes 1473
GPC3 LETM1 LZTS1 REST MPL ARID1B RPL18 MGMT GLI3 BIRC3 ZSWIM6 TRNS2 ETV6 HNF1B KIT BRCA1 SUFU PLAG1 SOX9 TP63 CTSC RASA1 ATRX TRIM37 SUFU BTK CYP11B1 NOTCH3 EPCAM PORCN PIGL AR TET2 FH TGIF1 HMBS ATRX TREX1 SMAD4 KRT17 FGFR1 WDPCP SF3B1 GPR101 KIT GLI1 SLC25A11 XRCC4 SDHD PRKCD RNF43 SDHB BAP1 EGFR PIGA NF1 ASCL1 MPL RET C2CD3 GDNF NR5A1 DICER1 TNFRSF4 CASP10 TERC FGF8 PSAP CIB1 SLC22A18 PTCH2 ENPP1 CDKN2C SLC25A11 GPR101 KIT AXIN2 TREX1 DYNC2LI1 ERCC4 RPS14 COMP TINF2 FOXE1 DHCR24 RPS7 TYROBP HOXD13 ERBB2 BLK EYA1 ZFPM2 ERCC6 NLRP1 STAC3 ERCC5 NUTM1 MEN1 WT1 BCL10 GNPTAB KRAS TP53 KDR PUF60 TRNF FCN3 SDHC KCNH1 MSTO1 EP300 BUB1B GNA11 KCNE3 DOCK8 SEMA3C ACD GLI2 SMPD1 SUFU NF1 PTCH2 ACAN DCC WT1 CTSA KIF11 BCR SRGAP1 KIT PTEN LEMD3 MLLT10 SCN4A BRCA2 BMPR1A NOTCH3 SEC23A CDKN1C BARD1 SPIB RSPO1 MC2R CALR ATP6V1B2 NBN RAD54L MST1 SUFU MYCN TMEM127 SRD5A3 IGF2 CD28 RUNX1 OGG1 HAX1 SDHC CTNNB1 MST1R SDHA IGF2 KCNJ10 IL12RB1 MEN1 RAD51 TFE3 ND5 MMEL1 MVK APC FLI1 RNF6 NF1 BRCA2 SUFU GPC6 NR4A3 TTC37 KIT NRTN BLNK IGH SPRED1 TXNRD2 IGF2R FOXP1 BUB1B SOS1 LRP5 GJB2 DNMT3A PMS2 PRKN RET MSH6 ACVRL1 MPLKIP ERCC2 AIP GNAS TAL1 NNT RECQL4 PMS1 DLL1 EIF2AK4 STAT6 MNX1 SDHB KRAS MEN1 MN1 SH2B3 EFL1 VHL KLLN RMRP RUNX1 SIX3 GDNF FANCD2 EXT1 CDH23 BRD4 DLEC1 NODAL CARMIL2 SDHB MSH2 HMBS SMAD4 SRP72 NRAS DOCK8 SPRTN BRCA1 MAP2K1 KRT14 LETM1 TERT MAP2K2 HRAS WHCR WT1 IDH1 TMEM107 SCN10A GJB3 SDHD KRAS GATA1 RPS20 GJB2 SLX4 USP8 PRKAR1A CR2 JAK2 HFE MPL POT1 BRCA2 GNAI3 SDHB ALK OCA2 TP53 GPC4 ACTG2 CTNNB1 HSPG2 AR FGFR1 STK4 MET TMC8 MRAP MSH6 CCBE1 EWSR1 LMO1 EDN3 LEMD3 PGM3 FGFR3 CASP8 RB1CC1 SCN9A FANCL TG SDHD COX3 IGF2 COL11A2 AGGF1 GPR101 PRKN PLCB4 SDHD NF1 GTF2E2 MAP2K1 ESCO2 CDC73 WRAP53 TET2 PDGFRB RNASEH2A RAD21 HNF1A TGFBR2 POLD1 COX2 TNFRSF10B MINPP1 DNAJC21 FAS EXT1 SLC26A2 APC SDHAF2 TINF2 LIG4 POLR1D WWOX TMC6 RPS19 ERCC2 SASH1 MC1R MVD SEC23B CYP2A6 GPC3 KIT HRAS RAD54L SDHA GDNF NKX2-1 GFI1 ALX3 STAT3 MYH11 DYNC2LI1 FGFR2 TCOF1 PTEN MAFA PIK3R1 SLC25A13 HRAS VHL COL7A1 GNAS FGFR2 PIK3CA GPC4 DICER1 ERCC3 PIK3CA RAD51C RB1 RMRP MLH3 ATM COL7A1 LIG4 NF1 VAMP7 RPL35A RB1 SETD2 BCL10 LPP NRAS KRAS ABCA5 ERCC2 PDE6D KCNQ1OT1 MS4A1 SLC22A18 APC LIG4 JAK2 FANCD2 GAS1 STAG3 NRAS PALLD SLC22A18 RFWD3 PPP2R1B APC PTPN11 PTEN WIPF1 PIK3CA NOP10 IL7 UROD TNFRSF1B TP53 REST SLC37A4 NHP2 CXCR4 KIT CYSLTR2 FZD2 ALX4 BMPR1A SRY TRNQ SDHD PIGL CCM2 FIBP FANCI GJB4 SPINK1 RPL10 NSD2 MAP3K1 RET CDK4 HSPA9 TET2 GFI1B MAD2L2 DCC AP2S1 SMAD7 BRCA2 TRNK ERCC3 BRCA1 ELANE SFTPC PTH1R COL1A1 FUZ OFD1 RET FLT4 PRKAR1A SBDS RPL26 SMARCE1 SMARCAD1 MSH2 BCR GPR35 INTU FANCA STAT1 ANTXR2 FGFRL1 TUBB BRAF SLX4 CASP10 TERT RAD21 MTOR TRIP13 MYD88 DPM1 RSPO1 PTPN11 CTNNB1 AIP PTEN VANGL1 CYP2D6 RPS10 GCK KRT16 DNAJC21 BCL2 AKT1 KRAS KLF6 NOTCH1 FLNA MAX NF2 PALB2 TP53 PSENEN RNF6 TSC1 HNF1B TP53 RFWD3 SDHD PERP TP53 DIS3L2 B3GALT6 STS PDGFB SMARCB1 BRAF BRIP1 CBFB BUB1 BLM INHBA CALR NBN MLH3 TAF1 MLF1 PIK3CA MSH2 CTLA4 ND6 PALB2 WT1 PTCH1 POLE ADA MC1R FLT4 ATP7A MLH3 SMO TRNF NRAS LMNA DLST TRNL1 MTAP TP53 ZAP70 SDHB CHEK2 PALB2 FLT4 CDK4 NBN MSR1 CC2D2A TNPO3 ECE1 RPS15A NAGS TMEM67 HNF1A PIK3CA ATP7A AKT1 NRAS SDHAF2 CXCR4 TSC2 NF2 EPHB2 WDPCP OFD1 BUB1 FLT3 APC SMARCA4 CDKN2A RPS29 MCM4 PDGFRA ESCO2 CTC1 ESR1 SDHB MSH6 APC HABP2 GNAQ KIF1B SH3GL1 CD70 MPL IGH ZIC2 GCM2 VEGFC HRAS CTNNB1 KCNH1 LRRC8A BRAF FAS ICOS NSD1 RNF43 AKT1 BIN1 DLC1 SH2B3 RARA WNT10A CARD14 SDHC EXOC6B ESCO2 POLR1C G6PC MSH6 KRT1 PDX1 TNFRSF13C ERCC3 EVC SNAI2 CD79A BRCA1 RNASEH2B CCND1 TP53 RPS19 H19 H19 BRCA2 TFAP2A ARMC5 FASLG FGFR3 APC F5 EDN1 MAP3K8 AIP APC AKT1 TERC CCND1 CEL MYC TP53 GPC4 ERCC5 HNF1A POLE DAXX NUP214 TRIP13 AKT1 TET2 CDC73 ND1 MUTYH PIK3R1 TERT CEBPA EXT2 OCRL DIS3L2 ADAR TGFBR2 BRCA2 MRE11 SOS1 HNF4A FAH TMEM127 WT1 AXIN2 TCF4 EDN3 PTPN3 KRAS SEMA4A PIK3CA XPA MFN2 TINF2 PIK3CA APPL1 RUNX1 GNPTAB FGFR3 NRAS PDCD10 RAG2 PTEN CTNNB1 SOX2 BMPR1A HBB TERT USP9X NFKB1 FANCC PRF1 WRN SRY SRSF2 PMS2 RHBDF2 PHOX2B RPS17 PAX3 RECQL4 KIF1B SQSTM1 RB1 EXT1 XPC CYLD TOP2A MYD88 CDKN1B TET2 GJB2 PTEN UBE2T RTEL1 PTCH1 KLHDC8B GATA1 POLH JAK2 RHOH FLCN DCLRE1C MTMR14 GTF2H5 PTEN SBDS TBC1D24 PAX7 AR TP53 ASPSCR1 MTM1 RECQL4 ERCC2 TGFBR2 ERCC4 JAK2 SF3B1 CDKN2B XPC GATA4 KIT POU2AF1 BRCA2 GREM1 CDON NTHL1 DICER1 GINS1 ATM RAD51D SHOX EXT1 RASGRP1 WT1 GATA2 NF2 ERCC4 TUBB MBTPS2 DHCR7 MYLK KCNN3 TCTN3 TMEM216 TMEM231 KRT1 CTNNB1 MPL PDGFRB FANCG RPGRIP1L KEAP1 DICER1 WT1 BAP1 FOXI1 ERCC4 CDKN2A FGFR3 KDSR CBL HRAS BMPR1A DISP1 RELA MAP3K1 PARN BCR ENG COL7A1 LMOD1 KRAS PAX6 SNAI2 GLI3 FANCF FOXO1 RPL15 TBX18 TRPV3 PIK3CA NRAS CDH1 GNAS SMARCB1 KLF11 ADA2 EDN3 POU6F2 CDH1 GNAS IL1B SMAD4 H19-ICR SDHB STK11 NF2 TRIM28 SEC23A SLCO2A1 BRCA2 BRAF DNMT3A MDM2 BMP2 BRCA2 DHH NRAS POU6F2 CTBP1 PTCH2 FLCN CALR BAP1 LIG4 HRAS REST BRAF SAMD9 NDP TYR KRT17 MUC5B PRSS1 MEN1 NPM1 ITK MSH2 CYLD TAL2 SRP54 IFIH1 HMMR TCTN3 ND5 JAK2 FAM20C RET NEK9 DMRT3 KRAS MINPP1 SH3KBP1 THPO FAH KRT5 JAK2 PHKG2 TSC1 TNFRSF13C MEN1 FH RPL31 FANCG PIK3CA IL2RG DNAJC21 VANGL2 MYO1H ALX1 CDKN2A AIP H19 NRAS TWIST1 PTEN TRNK TRPS1 RPS26 MAPRE2 RPS27 TCF3 KRT17 ERCC6 DHH MMP1 FGFR1 SEMA3D PTCH1 ABL1 CDKN2A SKI APC WWOX ZSWIM6 NF2 WNT10A KRAS GPC3 REST GJB6 HRAS VHL CTNNB1 TGFBR1 IL6 TDGF1 RPL11 IL1RN BRCA1 MGAT2 POT1 ASCC1 XPA TBX2 FLCN HFE NTHL1 SMARCB1 DVL3 TRNH IDH1 FANCA LAMB3 CD79B RAD51C PRDM16 PHOX2B GNAQ CCL2 PDGFRA CREB1 SRP54 PIEZO2 TRNL1 GBA GNAS WNT5A PIK3CA STS FANCB KRAS MAGT1 RAD51 IDH1 TNFRSF13B TREM2 GABRD BCL10 SKIV2L POLD1 KRIT1 KRAS ARSA SMAD4 RAD51 TP53 DIS3L2 KIAA0753 PRLR CD96 LZTR1 WRN GATA2 EDNRB MUTYH ATM CHIC2 TP53 CYLD PAX4 SLC26A4 RTEL1 VHL NEK1 TRNS1 GCM2 TYR ATP7B CTHRC1 BRAF ASXL1 OFD1 MLH1 CDKN1A PHOX2B XRCC2 CD19 RB1 FOXC2 TRIM28 EWSR1 TERT GNA11 F13B CDKN2A KARS1 BCL10 TP53 WT1 CDKN2A FDPS KIT COX1 COL14A1 VHL WT1 TERT SMAD4 STAR NUMA1 RPL5 PDGFB PCGF2 CFTR KCNQ1OT1 KIT GJA1 GNAQ CD27 FANCC IDH2 EVC2 BRCA2 TCF4 KRAS PIK3CA CDC73 ACVR1 BRIP1 TRNW PRCC GCGR CDKN1B STK11 SCN11A TGFBR2 AXIN2 ERBB2 RPL35 APC TSC2 IL12A SSX2 TET2 KIF1B DICER1 TRNP BTK CCDC22 PDGFRA ALX3 ADAMTS3 CD81 RET DKC1 GLI3 FGF3 SMAD4 STK11 ERCC6 WT1 ELANE C11ORF95 SAMD9L SLC45A2 NQO2 PTPN11 ATR PDGFRL TNFSF12 BRCA2 ADA BUB1B FASLG GDF5 KRAS CPLANE1 CREBBP CDC73 CLCNKB GATA2 CTRC SDHA ACTB APC BMPER SPINK1 APC2 MC1R FOXI1 DYNC2H1 KIT PPM1D SDHC NSD1 SDHC DDX41 ANTXR1 CASP8 F13A1 SUFU INS NUP214 ANTXR2 KIF7 NFKB2 ABCC8 TARS1 ERCC3 TCIRG1 ND4 ERCC2 GNAS TERT WASHC5 SLC49A4 RERE CALR MSH3 PHOX2B SLC25A13 BMPR1B CYLD SIX6 ASCL1 IDH2 FAN1 CHRNG CBL NEUROD1 MSH3 THPO VANGL1 CDKN2B TAF15 PTCH2 HMGA2 MSH6 CHEK2 FN1 GATA2 IRF1 KRAS BMPR1A NPM1 ERCC3 CDH1 ALK DNM2 ERBB3 PTPN11 DLST MUTYH PARN GFI1 NBN FGFR3 CHEK2 EP300 RNF113A TNFSF15 TEK TERF2IP ICOS COL18A1 TNFSF12 BRAF CHEK2 IFNG TMC6 USB1 KDM6B GJC2 SLC26A2 MDH2 TP53 ENG MLH1 KRT6B MNX1 PDGFB TRNH POLE CASP10 HPGD TET2 RB1 PHOX2B JAG1 GNB1 ACD TNFRSF13B MYC BRAF TSC1 SAMD9L BCL10 H19 POT1 USP8 IGF2 OFD1 CYP11B2 KCNQ1 CDH1 LMX1B TET2 ANTXR1 JAK2 SMARCB1 ELMO2 PTCH1 SIX1 L2HGDH WRAP53 BUB3 AXIN1 RET KCNJ11 ABL1 FANCE RAD54B FANCM TSC2 MAX IGHM TSC1 HACE1 CASR RNF139 MITF RAF1 WT1 TCTN3 POLH LIG4 TP53 KRT10 AAGAB SRY RAD50 TNFRSF1B TRNQ DNASE1L3 FAM149B1 KRT9 VHL FLCN TBXT SLC37A4 DKC1 PNP DDB2 SETBP1 ECM1 MSH2 CR2 COL2A1 COL7A1 MLH1 FH SFTPA2 PIK3CA FOXH1 MET HNF4A H19 KAT6B GPR143 PHB PMS1 ATP7A FAT4 TJP2 TFAP2A GDF2 AHCY TSC2 CD19 TRNS1 BDNF TRIP13 AKT1 FGFR2 RAG1 BRCA1 SDHC MLH1 XRCC3 NSD2 LMNA SDHC TERC EXT2 PIK3CA MSH3 SDHD SRC CHEK2 C1S ABCA5 HBB RYR1 FGFR2 CDC73 KIT FANCE RET LYST KCNJ10 BCHE HDAC4 INPP5E CRKL PHOX2B BAP1 CPLX1 PDGFRB ARL6IP6 RNASEL SETBP1 CTLA4 PALB2 DCLRE1C NSUN2 XIAP TRNS2 BMPR1A IL7R BCL6 COL4A5 PIK3CA NOD2 PRKAR1A NELFA IL2RG MYH8 RHBDF2 IGLL1 PIK3CA SERPINA1 FOXE1 ARHGAP26 TCF4 MITF ABCB11 ERBB2 GNA14 SLC26A2 NSD1 SH2B3 STK11 PTCH1 GDNF RPL27 DHCR7 WAS CIB1 SHH CACNA1S LIN28B SF3B1 ATM PRKCD RPS24 LAMA3 ATRX CASP8 AKT1 OPCML HFE SH2D1A ING1 CCND1 SLC12A3 HABP2 H19 LAMC2 RAD51C NAB2 NRAS MAPK1 CPLANE1 CYP26C1 CDKN1B CHD7 IGH MYF6 BLM ASXL1 FH NEK1 HLA-DRB1 SLC26A4 RPS14 SHOX RNASEH2C SMARCD2 GATA2 CDH23 WT1 EPCAM NR0B1 KLLN DVL1 SEC23B GPC3 SLC17A9 BRCA1 SRP54 DKC1 RECQL4 CD28 PTPN11 HRAS NBEAL2 BARD1 MLH1 DDB2 PMS2 IRF1 ABCC6 EXT2 ASXL1 TSR2 PTEN MALT1 PTEN BCR PALB2 BRIP1 SSX1 PHKA2 FGFR2 SDHB FERMT1 KCNAB2 FLT3 PMVK MSTO1 CEP57 MMP1 PICALM IRF5 TP53 PTPRJ RNR1 WWOX PLCD1 RPS28 FGFR3 COL2A1 IKBKG TERT RASA1 SAMHD1 PHF21A
Sarcoma
Genes 197
REST RB1 SDHC KRAS PAX7 ABCA5 ASPSCR1 RECQL4 SUFU APC ANTXR2 FH GREM1 KRT17 EXT1 PIK3CA BMPR1B RASGRP1 KIT SDHD PRKCD REST KCNN3 IDH2 NF1 CTNNB1 PDGFRB CDKN2B KEAP1 DICER1 DICER1 TAF15 CDKN2A FGFR3 SLC22A18 PTCH2 CDKN2C NBN CHEK2 EP300 AXIN2 CHEK2 IFNG PTH1R COL1A1 FOXO1 TBX18 GJC2 FLT4 PRKAR1A DHCR24 MSH2 MLH1 ANTXR2 GNAS CASP10 TRIP13 NUTM1 MDM2 TSC1 PTEN KCNH1 BUB1B FLNA NF2 ELMO2 NF1 BUB3 DCC MEN1 TSC1 MSH2 TP53 PTEN FAM20C PDGFB BUB1 NOTCH3 ATP6V1B2 TSC1 SUFU FLCN WT1 MSH2 MEN1 FH NRAS MTAP APC NF1 CHEK2 NR4A3 NBN APC NF2 TSC2 IL6 SPRED1 AKT1 NRAS BUB1B SOS1 FLCN SDHC SMARCB1 IDH1 LMNA MSH6 SDHC TSC2 NF2 SRC BUB1 APC RECQL4 ABCA5 SDHB GNAS APC PDGFRB VEGFC HRAS KCNH1 FAS BRD4 PRLR DLC1 SDHB PIK3CA WRN TP53 MAP2K1 IDH1 BRAF MLH1 CDKN1A RPS19 FOXC2 EWSR1 PTCH1 APC AKT1 CDKN2A KIT TP53 PDGFB AKT1 MSH6 EWSR1 CDC73 KIT NRAS IDH2 EXT2 CDKN1B SOS1 NF1 KLLN APC TSC2 SSX2 SEC23B DICER1 PIK3CA PDGFRA FAS EXT1 APC RECQL4 HRAS MLH1 CTNNB1 BMPR1A PMS2 EXT2 WRN PTEN SSX1 SDHA PTPN11 SDHB BUB1B PAX3 FASLG GDF5 CEP57 SQSTM1 CDC73 EXT1 TP53 PTPRJ CDKN1B PLCD1 RB1 APC PTCH1 MC1R
Mastocytosis
Genes 8
KIT ASXL1 KIT TET2 KIT KIT KIT SRSF2