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 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:Gastrointestin 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


HP:0002664: Neoplasm
Genes 1489
WHCR ATP7A PHOX2B KRT17 IL2RG HMGA2 PORCN KRAS TET2 IDH2 FLT3 ERCC4 AR BRCA1 BRCA2 GATA1 TCF4 TCTN3 GPR101 SMAD7 KRT6B PIK3CA KCNJ10 MAP2K2 REST TTC37 MC2R TRPS1 SIX6 ALX4 PIK3CA BRAF TP53 STK11 TSR2 EXT2 EDN1 RNF43 TRNL1 ATM SDHC EXT1 BCL10 BAP1 NF1 OCRL TP53 CHD7 TINF2 ERCC6 NF1 MAFA PMS2 ASXL1 PHOX2B CTNNB1 CR2 RET TCTN3 C11ORF95 PTPN3 PIEZO2 ABCB11 SETBP1 PDCD10 LRP5 LMOD1 MALT1 ASXL1 LZTR1 TINF2 RAD51C RECQL4 MAP2K1 FOXO1 PTCH2 RPS20 FLI1 BMPR1A SMARCAD1 BMPR1A MAP3K8 DNASE1L3 SUFU TP53 FOXP1 PTCH1 PDGFRB ND1 PIK3CA ZSWIM6 SETD2 INS NRAS HBB MEN1 AIP CLCNKB RPS10 HFE COX2 TSC2 DHH CTRC MEN1 EYA1 BRCA1 GINS1 MSH3 GLI2 TRNS1 HABP2 SSX1 SUFU PRKN CD81 TNFSF12 MYH11 KIT VEGFC WWOX H19 SDHD FGF3 TNFRSF1B RMRP XRCC2 HRAS MTM1 EPHB2 PLCD1 NBN CDKN1B TUBB RECQL4 EDNRB VHL ACAN MSH6 CDKN2B DCC TJP2 HRAS CDKN2A VHL REST NKX2-1 ANTXR1 RPL35 DNM2 FGFR3 SNAI2 NLRP1 ACTG2 GNB1 EWSR1 CBFB NSD1 FLCN ERBB2 MLH1 H19 EIF2AK4 RPL10 TMEM107 TRNK RAD54L RAD51C INPP5E NFKB1 CDKN1A KDM6B F13B SLC26A2 TRNS1 RPL26 CYLD H19 PTEN PTPN11 DCLRE1C MPL FLCN NEK1 MITF MSH3 NUTM1 IL7 STAT3 TRNS2 TG ERCC3 MNX1 NRAS MLH3 TSC1 GLI3 CDK4 SDHC NF1 BRCA2 CIB1 ATRX BRCA2 ADAMTS3 ZFPM2 COL2A1 TET2 ZIC2 SLCO2A1 BLM GJA1 MAP3K1 PIK3CA SDHA RTEL1 CDK4 KCNH1 SH2B3 APC ESCO2 FANCC TERT USP9X APC RAD54B NF2 SDHB RPS14 PPP2R1B RPS19 RPL35A MSH2 WRAP53 RASA1 LMNA ACVRL1 POLH SDHB DIS3L2 PIGA GNPTAB CXCR4 MSH2 SLC25A13 BMP2 NNT PSENEN FOXI1 APC IL1RN MITF ACD PTEN MPL RUNX1 ERCC3 ERCC4 DLEC1 CHEK2 BRCA2 JAK2 SBDS BRCA1 SDHD SEMA3D MSH6 HFE TREM2 APC CCDC22 MINPP1 DISP1 FAM20C MAP2K1 ALK BRCA1 STIM1 SLC25A13 RFWD3 HRAS GLI1 TET2 DVL3 COL7A1 HMBS TFAP2A ICOS CALR PTEN UROD DKC1 FDPS LIG4 TXNRD2 SRSF2 ND5 SDHD CHEK2 NRAS BCL6 GPC3 XPC MEN1 ERCC2 AXIN2 MYC RAD51 GBA KIF1B SDHB EXT2 EXT2 NTHL1 SRY RPGRIP1L MPL MTOR CASP8 RB1CC1 IGF2 FANCC ERCC4 WRN PGM3 VHL ING1 PLAG1 WT1 MYLK KLLN PIK3CA G6PC RPS7 MCM4 ANTXR1 POLH BRCA2 DLL1 OGG1 WRN F13A1 SBDS EFL1 TAF15 GLI3 GPC3 KRAS CDKN2B MAPK1 DIS3L2 GPR101 NRTN DKC1 KLLN NSUN2 MAP3K1 ERBB2 PHKG2 SRGAP1 CYLD NBN ALK MAX WT1 ACTB PALB2 TBX18 FIBP CASP10 DVL1 TYR MSH2 RECQL4 PIGL EDN3 WT1 ATP7B RPL27 RET USP8 FGFR2 PDGFRL H19 CCND1 ATM AXIN2 COL7A1 AKT1 TERT MUTYH HOXD13 DICER1 THPO GDF5 CEL SDHB EXT2 SRP72 TERT TRNF TP53 LIN28B APC NPM1 FGFR3 PTEN SMPD1 SLC22A18 SDHC PRDM16 KIT STK11 RPL11 LETM1 CALR SDHC RB1 PIK3CA PLCB4 COL4A5 CASP8 SKI H19 COL1A1 CC2D2A CASP10 GCGR GLI3 PIK3CA RPS29 RSPO1 PTEN MYSM1 BAP1 SRY UBE2T BRCA1 USP8 COL7A1 RNASEH2B KIF1B MN1 RELA SMAD4 VHL SH3KBP1 BCR CD79B SRP54 SRP54 SSX2 CHRNG RPL18 NF1 WWOX RERE LZTS1 WT1 MSH3 TYROBP ASCL1 IKBKG ABCC6 FAH KIT GDNF FANCE TERT BIN1 FANCL KIF11 SDHB WDPCP SLC6A17 TP53 HNF1A KEAP1 POLE HSPA9 SMO PTCH2 PTCH1 PMS1 ELMO2 BCL2 NSD2 EXT1 SRD5A3 STAT6 MVD TERC SF3B1 MNX1 FGFR1 CYSLTR2 POU2AF1 SMARCB1 NOD2 GJB2 SDHC FLT4 KRT9 CDH1 IRF1 SEC23B MYCN MGMT RPL10 RPL5 KIF7 TCF3 KRAS MUTYH TMEM127 KRAS IGH CTSC GNAS CD28 WWOX HNF1A BUB1B MC1R WNT10A CBL WT1 BRAF ADAR GAS1 GTF2E2 SMARCB1 RPS17 PARN TMEM127 BRIP1 SHH SRC GNAI3 STAR GDNF SLC22A18 FOXH1 SNAI2 GPC4 TNFRSF13C KARS1 TBC1D24 BMPR1A TET2 CD27 CASP8 DHCR7 KDSR HNF1A SH3GL1 PNP USB1 TSC2 TRIP13 TMEM67 EDN3 PMS1 PTPN11 GNA11 CREB1 ADA RAG2 PRSS1 KCNQ1 GPR101 PRF1 MTAP FANCA MSH6 TRNQ BRCA2 KRT1 RNASEL POU6F2 ACD SCN9A APC NSD2 INTU BRAF POU6F2 BRCA2 RB1 GTF2H5 PIK3CA FANCM TARS1 BRAF CASR RET VHL GPR143 TRNP GCM2 TMEM231 CPLANE1 RPS15A SOX9 GFI1B EPCAM MEN1 TERT KRAS SDHAF2 NF1 TRIP13 GATA2 SLC26A4 APC MPLKIP SAMD9L IL6 GNAS IGH AKT1 FANCD2 ESR1 SDHA APC MYF6 RASGRP1 SMAD4 MLLT10 LIG4 CPLANE1 BRCA2 MC1R MRE11 DLST SUFU LMO1 SDHB ABCA5 RMRP SDHC NUP214 AKT1 SMARCD2 DLC1 C1S TRNW THPO CHEK2 KIT SLC37A4 BCHE KCNJ11 ARID1B APC2 SAMD9 TMC6 SLX4 TNFRSF13B FGFR1 TRNH RAD21 KCNN3 DKC1 VANGL1 AXIN2 TCOF1 RPS19 SLC26A2 GPR35 CR2 TFAP2A KRAS FGFR3 PRKCD JAK2 EGFR AIP CTNNB1 KCNJ10 FANCI LYST TET2 SLC25A11 TP53 TCTN3 MUTYH ANTXR2 SEMA3C MMP1 AKT1 PDX1 JAK2 TCIRG1 PTCH1 MUC5B EXT1 DNMT3A BMPR1A SERPINA1 FAN1 CDC73 PTCH2 PIK3CA H19 FERMT1 GPC3 RET RET APC PALLD LPP BRD4 GNAS BMPR1B MAPRE2 DICER1 CTC1 TAL1 DICER1 STK11 HRAS GATA1 BCL10 KCNE3 XRCC4 HNF4A BDNF KLF11 SF3B1 MLH3 GNAQ TRPV3 IGLL1 PAX7 CRKL GDNF GATA2 ARL6IP6 ENG PTCH1 NEK9 TSC1 RNF139 ERCC3 PDGFRA IL2RG CTHRC1 WT1 BAP1 ATP7A SRP54 ABCC8 ESCO2 GPC4 OFD1 TNFSF15 APPL1 RNF6 CTSA TNFRSF1B TP53 PHOX2B DCLRE1C DDB2 BCL10 BCR KRT14 ALX3 EVC2 CD70 SMARCB1 AHCY SDHAF2 RAD51D SPINK1 SDHD ATM GABRD WT1 FASLG CTBP1 NOTCH1 NF2 DPM1 ERCC6 STS PHOX2B BUB1 FLT4 L2HGDH LAMC2 NTHL1 STAG3 ENG SDHD CTNNB1 DAXX NRAS MST1 MSTO1 SLC26A4 RAF1 STS FGFR3 EXOC6B VAMP7 NELFA HRAS ANTXR2 LEMD3 TNFSF12 GPC4 MLH1 SMAD4 RAD50 SUFU TRIP13 REST GNAS CBL RHBDF2 ASXL1 SMAD4 TCF4 ERCC6 WT1 BRAF APC TRIM28 TERT DNAJC21 RPL15 PAX3 SETBP1 CDH1 GNAS SMARCB1 AKT1 ASCL1 KRAS NAB2 ERCC5 RECQL4 KRAS DNMT3A EDN3 POLD1 FAM149B1 CDKN1C KRAS TP53 SMARCE1 PTEN PALB2 SEMA4A TEK NBN NHP2 GPC3 ETV6 FGF8 COL11A2 SMAD4 RNASEH2A NRAS MC1R TDGF1 FGFRL1 FGFR1 CTNNB1 IGH DNAJC21 CCND1 RET DIS3L2 DHCR24 CARD14 BRCA2 SQSTM1 NFKB2 TRNQ NDP SFTPA2 PAX4 COL7A1 TP53 RSPRY1 IFNG HMMR PALB2 FAT4 MBTPS2 MDM2 KRAS GNAS C2CD3 POT1 ABL1 WNT5A FANCE ABL1 ICOS SDHD RAD21 NSD1 SOS1 IL12A LIG4 PIK3CA TBXT RAD51 EWSR1 FZD2 FLNA BRCA2 NRAS TWIST1 TET2 TSC1 INHBA CAT CTNNB1 PIGL IRF1 PTCH2 TRNH MLH1 GFI1 CDC73 RET FANCD2 EVC NF2 TNPO3 SOX2 DYNC2H1 HRAS NEK1 CCND1 KRT10 AKT1 KIT PALB2 VHL CYLD IL1B GJC2 MLH1 SDHC FGFR2 CYP2A6 FOXE1 ARMC5 ERCC2 SLC25A11 LAMA3 FLCN BRCA1 BIRC3 MVK TOP2A PDGFB TCF4 RFWD3 ATP6V1B2 GDNF GATA4 CTNNB1 CDKN1B C2CD3 BRCA2 FUZ STK11 AKT1 FGFR2 SHOX TGFBR1 BTK LEMD3 FIBP SF3B1 SUFU PRLR NR5A1 FN1 ERBB2 CD19 RNR1 PTPN11 KIT RAD51 WAS PTEN TGFBR2 RPS24 CYLD RNF113A MYO1H ALX3 JAK2 BLM CTNNB1 CDKN2A PARN SH2B3 POLD1 CHEK2 COX1 KRT1 EXT1 BRAF PRCC MSH2 GATA2 REST NRAS RB1 TINF2 BMPR1A NR4A3 AGGF1 SIX3 RAG1 ND4 COL2A1 CDKN2A SDHD TREX1 WNT10A SEC23B XPA MET TP53 CDKN1B RPS27 PCNA HMBS RPS26 KIT FGFR2 TRIM37 HPGD ERCC5 PAX6 SLX4 PICALM PSAP FCN3 BMPR1A USF3 XPC DNAJC21 KRT16 BUB3 H19-ICR GPC6 STAC3 RPS28 FANCA RNF43 AP2S1 PDGFB DYNC2LI1 CYP11B1 ABCA5 PTCH1 TERF2IP KRAS DYNC2LI1 CDH1 CDC73 TERC SPRED1 PDGFB TRNF MTMR14 MAD2L2 FOXI1 ERCC2 GJB4 KAT6B MSH6 FASLG KRAS SEC23A RUNX1 CD19 WASHC5 KIT HLA-DRB1 WRAP53 FLT3 CEP57 KDR TREX1 TMEM216 PDGFRA ERCC3 KIT NOTCH3 WIPF1 TERC CTLA4 NQO2 CDKN2A RSPO1 STK4 PTPN11 GJB2 KRAS MET SPINK1 PDGFRB RHOH BUB1 ND6 CDKN2C TFE3 EP300 CHIC2 HNF1B NUMA1 BRCA1 SRY FLCN MLH3 SCN10A GNPTAB KRAS NODAL TGFBR2 PPM1D DOCK8 EPAS1 PHOX2B OCA2 KCNQ1OT1 CYP2D6 ITK DICER1 PRKCD ASPSCR1 SUFU IDH1 RUNX1 ATRX FOXC2 MFN2 SAMD9L SCN4A KIF1B DHH POLE VHL POLR1D KCNAB2 BRAF SLC12A3 CARMIL2 ENPP1 NRAS LRRC8A KIT SH2B3 MST1R CEBPA NRAS MRAP TP53 ND5 FH LAMB3 CALR SLC37A4 PERP KLHDC8B FH SFTPC TGIF1 CHEK2 SLC17A9 SLC22A18 TERT CDH23 MDH2 KRT17 PTEN FGFR3 RB1 YY1 ELANE EP300 SPRTN GJB3 XPA IDH2 MAGT1 ATR GNA14 OFD1 IL7R GREM1 ESCO2 HRAS PRKAR1A MMP1 TP53 KRT17 COL14A1 RHBDF2 MPL OFD1 RYR1 IFIH1 SCN11A IDH1 JAK2 WT1 TP53 ARSA LIG4 CCBE1 FANCG KCNH1 ELANE COL18A1 HACE1 NUP214 MYC CD79A AR CDH1 BRIP1 WT1 BCR BUB1B ERCC3 KRIT1 NBN IGF2 FANCF PDGFRA BLNK PCGF2 MSH6 MEN1 FAS BRIP1 PTH1R SIX1 RNF6 BRAF DHCR7 BMPER BUB1B TP53 RET CTLA4 HABP2 ARHGAP26 DLST GCK ERCC2 RAD54L POLE HSPG2 GNA11 ADA SMAD4 BCL10 RB1 STAT1 TAF1 RPS14 BCR IL12RB1 IRF5 TMC8 TNFRSF13B CYP26C1 CALR POT1 MINPP1 POLR1C CD28 ATP7A HNF1B ERCC2 ACVR1 RPL31 VANGL1 TP63 ERCC4 SLC45A2 OFD1 LMX1B PIK3CA ASCC1 TET2 IGF2R BARD1 TUBB IGF2 BTK MSTO1 CIB1 PHB CDKN2A TNFRSF10B KIAA0753 TBX2 FOXE1 EPCAM TNFRSF13C SLC26A2 ATRX MGAT2 SKIV2L CXCR4 PIK3R1 RTEL1 TSC1 HAX1 SDHB PRKAR1A DDB2 GFI1 CDH23 XRCC3 PMVK TP53 PIK3CA GJB2 NF2 KLF6 AR ZSWIM6 SDHB CDC73 PIK3CA CCND1 GJB6 ATM SOS1 NOTCH3 DDX41 TSC2 FLT4 FGFR3 RASA1 GDF2 F5 PMS2 PTEN HBB TSC2 CASP10 ADA2 AIP WT1 LETM1 PNP COMP TRIM28 TP53 PALB2 RAD51C CCL2 CDC73 SH2D1A COX3 ZAP70 PIK3CA CYP11B2 PDGFRB PTPN11 PHOX2B FH KIT HNF4A RNASEH2C MYD88 PDE6D JAG1 TYR SEC23A FH NPM1 PHKA2 DICER1 PIK3CA HFE GNAQ DMRT3 MS4A1 MYH8 VANGL2 SHOX PUF60 GATA2 BAP1 B3GALT6 TRNS2 HRAS HDAC4 FANCG SAMHD1 GATA2 LIG4 AXIN1 TNFRSF4 OPCML PRKN FGFR2 ECM1 TGFBR2 LMNA WDPCP KCNQ1OT1 BLK GCM2 ALX1 NRAS KIT AAGAB FAH MAX RARA NEUROD1 TGFBR2 MYD88 PHF21A IDH1 MLH1 FANCB CPLX1 SMARCA4 EXTL3 AIP TERT BCL10 XIAP IGF2 SASH1 PIK3R1 PTEN NAGS TMC6 NBEAL2 NOP10 JAK2 SDHB MSH2 ECE1 BARD1 APC PMS2 CCM2 JAK2 MMEL1 RET SDHA SDHD IGHM CACNA1S FAS NR0B1 POT1 SPIB TAL2 NF2 CDON WT1 TET2 PTPRJ CD96 TRNL1 DOCK8 DCC MPL GNAQ CREBBP CDKN2A TRNK MSR1 KRT5 PRKAR1A ERBB3