A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer

Description

This phase 1/2 study will evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR/HER2 Inhibitor TAK-788 in participants with NSCLC and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations. The trial will be conducted in three parts: a dose escalation (Part 1), including Part 1A (dose escalation combination component of TAK-788 in combination with Pemetrexed/Carboplatin) and Part 1B (TAK-788 monotherapy and TAK-788 in combination with pemetrexed/carboplatin with primary antidiarrhea prevention with loperamide.) and expansion phase (Part 2), followed by an extension phase (Part 3).

The objectives of the dose escalation phase (Part 1),dose escalation combination phase (Part 1A, only for selected sites in the United States) and Antidiarrhea Prophylaxis Cohorts ( part 1B, only for selected sites in the United States) are to determine the safety profile of orally administered TAK-788 and TAK-788 in combination with Pemetrexed/Carboplatin, including the MTD, DLTs, RP2D,pharmacokinetic profile and with loperamide as primary antidiarrhea prevention incidence and severity of TAK-788-associated diarrhea and anti-tumor activity of TAK-788 (Part 1B) . The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial).

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.

The extension phase will evaluate efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and who have been previously treated. The study will enroll approximately 395 participants.

Details