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 and its active metabolites, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2) mutations, explore relationship between tumor and/or plasma biomarkers and TAK-788 efficacy, safety, and/or cytochrome P450 (CYP) 3A induction (in Part 1 [Dose Escalation Component] and Part 2 [Expansion Cohorts] for oral TAK-788) and (in Part 1A [Dose Escalation Combination Component] when TAK-788 is taken in combination with pemetrexed/carboplatin), and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations in Parts 1 and 2.
Name: TAK-788
Name: Pemetrexed
Name: Carboplatin
Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Part 1A, Dose Escalation Combination Component: RP2D/MTD of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin Time: Up to Cycle 2 (Cycle length=21 days)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Part 1A, Dose Escalation Combination Component: Identify DLTs of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin Time: Up to Cycle 2 (Cycle length=21 days)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 and when TAK-788 Given in Combination With Pemetrexed/ Carboplatin Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results Time: Up to 36 months after first doseDescription: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, 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 for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of TAK-788 and its Metabolites Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, 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 for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, 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 for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, 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 for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, 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 for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Cmax: Dose Proportionality for TAK-788 Exposure Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.
Measure: Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: AUC: Dose Proportionality for TAK-788 Exposure Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)Allocation: Non-Randomized
Sequential Assignment
There are 5 SNPs
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 ---
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 ---
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 ---
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 ---
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 ---