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Report for Clinical Trial NCT03599518

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Gefitinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer

This study has two parts: dose escalation and dose expansion. The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study population - For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population. In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles. The number of treatment cycles is not fixed in this study. Participants will continue study treatment for 36 months unless they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).

NCT03599518 Non Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: DS-1205c

Description: DS-1205c 200 mg capsule for oral administration
Type: Drug
Group Labels: 1

DS-1205c with Gefitinib

Name: Gefitinib

Description: Gefitinib 250 mg tablet for oral administration
Type: Drug
Group Labels: 1

DS-1205c with Gefitinib


Primary Outcomes

Measure: Number pf participants with dose-limiting toxicities during the Dose Escalation period

Time: within 28 days

Description: An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

Measure: Number of participants with adverse events (AEs)

Time: within 36 months

Secondary Outcomes

Measure: Plasma concentration of DS-1205a versus time

Time: during the 7 day run-in period

Measure: Maximum observed analyte concentration (Cmax)

Time: during the 7 day run-in period

Measure: Actual sampling time to reach Cmax (Tmax)

Time: during the 7 day run-in period

Measure: Area under the analyte concentration versus time curve during a dosing interval (AUCtau)

Time: during the 7 day run-in period

Measure: Minimum observed analyte concentration prior to the beginning, or at the end, of a dosing interval (Ctrough)

Time: during the 7 day run-in period

Description: Categories: DS-1205a, gefitinib

Measure: Cmax during a dosing interval (Tau) at steady state (Cmax,ss)

Time: during the dose expansion period, within 36 months

Description: Categories: DS-1205a, gefitinib

Measure: Plasma concentration of DS-1205a versus time

Time: during the dose expansion period, within 36 months

Description: Categories: DS-1205a, gefitinib

Measure: Tmax

Time: during the dose expansion period, within 36 months

Description: Categories: DS-1205a, gefitinib

Measure: Ctrough

Time: during the dose expansion period, within 36 months

Description: Categories: DS-1205a, gefitinib

Measure: AUCtau

Time: during the dose expansion period, within 36 months

Description: Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.

Measure: Objective response rate (ORR), graded according to RECIST version 1.1

Time: within 36 months

Measure: Change from baseline in size of target lesion(s)

Time: within 36 months

Description: DOR is defined as the time from documentation of tumor response [either CR or PR] to disease progression

Measure: Duration of response (DOR)

Time: within 36 months

Description: DCR is defined as the sum of CR rate, PR rate, and stable disease (SD) rate

Measure: Disease control rate (DCR)

Time: within 36 months

Description: PFS is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic PD, or death due to any cause

Measure: Progression-free survival (PFS)

Time: within 36 months

Measure: Overall survival (OS)

Time: within 36 months

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 4 SNPs

SNPs


1 L858R

Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R ---

Has history of pancreatitis within the past 6 months Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R ---


2 L861Q

Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R --- --- L861Q ---

Has history of pancreatitis within the past 6 months Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R --- --- L861Q ---


3 T790M

Is willing to provide archival tumor tissue from a biopsy performed after progression during treatment with gefitinib, erlotinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy 9. Demonstrates absence of EGFR T790M mutation in tumor tissue since progression during gefitinib, erlotinib, afatinib, or osimertinib treatment 10. Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks Exclusion Criteria: 1. Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression 2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation - no new testing for these genomic alterations is required for Screening 3. Has received treatment with any of the following: 1. --- T790M ---


4 V600E

Is willing to provide archival tumor tissue from a biopsy performed after progression during treatment with gefitinib, erlotinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy 9. Demonstrates absence of EGFR T790M mutation in tumor tissue since progression during gefitinib, erlotinib, afatinib, or osimertinib treatment 10. Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks Exclusion Criteria: 1. Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression 2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation - no new testing for these genomic alterations is required for Screening 3. Has received treatment with any of the following: 1. --- T790M --- --- V600E ---



HPO Nodes


HPO: