Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAK-788 · 5 trials · 4 indications
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST Version 1.1 are met or death, whichever occurs first.
As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A for midazolam 3 mg oral solution.
As planned, this PK outcome measure was only assessed in Part A for midazolam 1 mg intravenous infusion.
| Arm | Type | Description |
|---|---|---|
| TAK-788 Group (Arm A) | EXPERIMENTAL | TAK-788 160 milligram (mg) with or without food, capsules, orally, once daily until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. |
| Platinum-based Chemotherapy Group (Arm B) | ACTIVE_COMPARATOR | Pemetrexed 500 milligram per meter square (mg/m\^2) plus cisplatin 75 mg/m\^2, infusion, IV, once on Day 1 of 21-day cycle pemetrexed 500 mg/m\^2 plus carboplatin, infusion, IV, once at a dose calculated to produce area under curve (AUC) of 5 milligram\*minute per milliliter (mg\*min/mL) on Day 1 of 21-day cycle until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. Pemetrexed/cisplatin or pemetrexed/carboplatin will be repeated every 3 weeks for 4 cycles, followed by maintenance treatment with pemetrexed 500 mg/m\^2, on Day 1 of a 21-day cycle thereafter. |
| Part A: Midazolam + TAK-788 | EXPERIMENTAL | Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with TAK-788 160 mg, capsule, orally, once daily from Day 3 through 30 in Cycle 1. |
| Part B: TAK-788 | EXPERIMENTAL | TAK-788 160 mg, capsules, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 24, or until progressive disease (PD), intolerable toxicity, or another discontinuation criterion is met, whichever is sooner. Eligible participants from Part A may enter into Part B. Based on the investigator's opinion, if a participant continues to experience clinical benefit, treatment with TAK-788 may be continued after PD. |
| TAK-788 160 mg Fasted + TAK-788 160 mg Fed | EXPERIMENTAL | TAK-788 160 milligram (mg), capsule, orally, once on Day 1 of Period 1 under fasted conditions (Treatment A), followed by 10 days washout period, followed by TAK-788 160 mg, capsule, orally, once on Day 1 of Period 2 under fed conditions (Treatment B). |
| TAK-788 160 mg Fed + TAK-788 160 mg Fasted | EXPERIMENTAL | TAK-788 160 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (Treatment B), followed by 10 days washout period, followed by TAK-788 160 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions (Treatment A). |
| Part 1 Cohort 1: TAK-788 | EXPERIMENTAL | TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1. |
| Part 1 Cohort 2: TAK-788 | EXPERIMENTAL | TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 1. |
| Part 1 Cohort 3: TAK-788 | EXPERIMENTAL | TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 2. |
| Part 1 Cohort 4: TAK-788 | EXPERIMENTAL | TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 3. |
| Part 1 Cohort 5: TAK-788 | EXPERIMENTAL | TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 4. |
| Part 2: TAK-788 Fed + TAK-788 Fasted | EXPERIMENTAL | TAK-788, capsule, orally, once on Day 1 of Intervention Period 1 under fed conditions with low-fat meal (Treatment A), followed by at least 7 days washout period, further followed by TAK-788, capsule, orally, once on Day 1 of Intervention Period 2 under fasted conditions (Treatment B). TAK-788 dose will be determined based on review of safety and tolerability data from cohorts of Part 1. |
| Part 2: TAK-788 Fasted + TAK-788 Fed | EXPERIMENTAL | TAK-788, capsule, orally, once on Day 1 of Intervention Period 1 under fasted conditions (Treatment B), followed by at least 7 days washout period, further followed by TAK-788, capsule, orally, once on Day 1 of Intervention Period 2 under fed conditions with low-fat meal (Treatment A). TAK-788 dose will be determined based on review of safety and tolerability data from cohorts of Part 1. |
| Part 3: TAK-788 DiC (reference) + TAK-788 DiC (test) | EXPERIMENTAL | TAK-788 160 mg, DiC A (reference), orally, under fasted condition, once on Day 1 of Intervention Period 1, followed by at least 7 days washout period, further followed by TAK-788 160 mg, DiC B (test), orally, under fasted condition, once on Day 1 of Intervention Period 2. |
| Part 3: TAK-788 DiC (test) + TAK-788 DiC (reference) | EXPERIMENTAL | TAK-788 160 mg, DiC B (test), orally, under fasted condition, once, on Day 1 of Intervention Period 1, followed by at least 7 days washout period, further followed by TAK-788 160 mg, DiC A (reference), orally, under fasted condition, once on Day 1 of Intervention Period 2. |
| Part 1: Dose Escalation Component | EXPERIMENTAL | TAK-788 treatment for participants with advanced NSCLC. |
| Part 2: Expansion Cohort 1 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR tyrosine kinase inhibitors (TKI), and who have no active, measurable central nervous system (CNS) metastases. |
| Part 2: Expansion Cohort 2 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases. |
| Part 2: Expansion Cohort 3 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases. |
| Part 2: Expansion Cohort 4 | EXPERIMENTAL | TAK-788 treatment for 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. |
| Part 2: Expansion Cohort 5 | EXPERIMENTAL | TAK-788 treatment for 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. |
| Part 2: Expansion Cohort 6 | EXPERIMENTAL | TAK-788 treatment 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 |
| Part 2: Expansion Cohort 7 | EXPERIMENTAL | TAK-788 treatment for participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active without active CNS metastases. |
| Part 3: Extension Cohort | EXPERIMENTAL | TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. |
| Name | Type | Description |
|---|---|---|
| TAK-788 | DRUG | TAK-788 capsule |
| Pemetrexed | DRUG | Pemetrexed IV infusion |
| Cisplatin | DRUG | Cisplatin IV infusion |
| Carboplatin | DRUG | Carboplatin IV infusion |
| Midazolam | DRUG | Midazolam Oral Solution and Midazolam Intravenous Infusion. |
| Placebo | DRUG | TAK-788 placebo-matching capsules. |
Inclusion Criteria: * Male or female adult patients (aged 18 years or older) * Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC * Documented epidermal growth factor receptor (EGFR) in-frame exo...