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Report for Clinical Trial NCT02716116
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
The purpose of this phase 1/2 study is to evaluate the safety, recommended phase 2 dose
(RP2D), dose limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics of
oral TAK-788, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth
factor receptor (EGFR) or human epidermal growth factor 2 (HER2) and anti-tumor activity of
TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations, and
to explore relationship between tumor and/or plasma biomarkers, and TAK-788 efficacy, safety,
and/or cytochrome P450 3A (CYP3A) induction. The study will also determine the efficacy of
TAK-788 in participants with locally advanced or metastatic NSCLC harboring EGFR in-frame
exon 20 insertion mutations who have received at least 1 prior line of therapy for locally
advanced or metastatic NSCLC.
Name: TAK-788
Description: TAK-788 capsules.
Type: Drug
Group Labels: 9 Dose Escalation Cohort Expansion Cohort 1 Expansion Cohort 2 Expansion Cohort 3 Expansion Cohort 4 Expansion Cohort 5 Expansion Cohort 6 Expansion Cohort 7 Extension Cohort
Primary Outcomes
Measure: Dose Escalation Cohort: RP2D of Orally Administered TAK-788 Time: Day 1 to 28 (Cycle 1)
Measure: Expansion Cohorts 1, 2, 4, 5 and 7: Confirmed Objective Response Rate (ORR) Assessed by the Investigator Time: up to 36 months after first dose
Measure: Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC) Time: up to 36 months after first dose
Measure: Extension Cohort: Confirmed ORR Assessed by IRC Time: up to 36 months after first dose
Measure: Expansion Cohort 6: Confirmed ORR Assessed by IRC Time: up to 36 months after first dose
Secondary Outcomes
Measure: Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results Time: up to 36 months after first dose
Measure: Dose Escalation Cohort: Identify DLTs and MTD of TAK-788 Time: Day 1 to 28 in Cycle 1 (Cycle length is equal to [=] 28 days)
Measure: Dose Escalation and Expansion Cohorts: Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: AUC 24: Area Under the Concentration-time Curve from Time Zero to 24 hours for TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: AUCt: Area Under the Concentration-time Curve from Time Zero to Time t for TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: RAC (Cmax): Accumulation Ratio Based on Cmax of TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: Ctrough: Observed Concentration at the end of a Dosing Interval of TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: Cmax: Maximum Observed Concentration of TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC Time: up to 36 months after first dose
Measure: Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion Cohort 3: Duration of Intracranial Response (iDOR) Time: up to 36 months after first dose
Measure: Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC Time: up to 36 months after first dose
Measure: Expansion Cohort 3: Intracranial PFS (iPFS) Time: up to 36 months after first dose
Measure: Expansion and Extension Cohorts: Overall Survival (OS) Time: up to 36 months after first dose
Measure: Extension Cohort: Confirmed ORR as Assessed by the Investigator Time: up to 36 months after first dose
Measure: Dose Escalation and Expansion Cohorts: Cmax: Dose Linearity for TAK-788 Exposure Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Dose Escalation and Expansion Cohorts: AUC: Dose Linearity for TAK-788 Exposure Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)
Measure: Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and Health-related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) Time: up to 30 days after last dose of drug (approximately up to 37 months)
Measure: Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and health-related Global Quality of Life (HRQoL) Based on Quality of Life Questionnaire Lung Cancer Module-13 (QLQ-LC13) Time: up to 30 days after last dose of drug (approximately up to 37 months)
Measure: Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator Time: up to 36 months after first dose
Purpose: Treatment
Allocation: Non-Randomized
Sequential Assignment
There are 5 SNPs
SNPs
1 L858R
Part 2: Expansion Cohort 4 Specific Inclusion Criteria:
1. Have one of the following documented by a local test: an activating mutation in EGFR
including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or
an uncommon activating mutation other than exon 20 insertion including, but not
limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R ---
2 L861Q
Part 2: Expansion Cohort 4 Specific Inclusion Criteria:
1. Have one of the following documented by a local test: an activating mutation in EGFR
including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or
an uncommon activating mutation other than exon 20 insertion including, but not
limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M --- --- S768I --- --- L861Q ---
3 L861R
Part 2: Expansion Cohort 4 Specific Inclusion Criteria:
1. Have one of the following documented by a local test: an activating mutation in EGFR
including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or
an uncommon activating mutation other than exon 20 insertion including, but not
limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M --- --- S768I --- --- L861Q --- --- L861R ---
4 S768I
Part 2: Expansion Cohort 4 Specific Inclusion Criteria:
1. Have one of the following documented by a local test: an activating mutation in EGFR
including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or
an uncommon activating mutation other than exon 20 insertion including, but not
limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M --- --- S768I ---
5 T790M
Part 2: Expansion Cohort 4 Specific Inclusion Criteria:
1. Have one of the following documented by a local test: an activating mutation in EGFR
including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or
an uncommon activating mutation other than exon 20 insertion including, but not
limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M ---
The seven expansion cohorts will be:
1. NSCLC participants with EGFR exon 20 activating insertions, who have either not received
or not shown an objective response to an EGFR TKI, and who have no active, measurable
CNS metastases;
2. NSCLC participants with HER2 exon 20 activating insertions or point mutations and no
active, measurable CNS metastases;
3. NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating
insertions or point mutations and active, measurable CNS metastases;
4. NSCLC participants with other targets against which TAK-788 is active (examples include
EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and
other uncommon EGFR activating mutations), without active CNS metastases;
5. NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an
objective response to an EGFR TKI and subsequently progressed, without active CNS
metastases;
6. NSCLC participants with EGFR exon 20 activating insertions, who have not received prior
systemic anticancer treatment for locally advanced or metastatic disease, without active
CNS metastases; and
7. Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which
TAK-788 is active, without active CNS metastases. --- T790M ---
HPO Nodes
HPO: