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

Summary

Objectives

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), expansion phase
(Part 2), followed by an extension phase (Part 3).

The objectives of the dose escalation phase (Part 1), is to determine the safety profile
of orally administered TAK-788, including the MTD, DLTs, RP2D, pharmacokinetic profile.
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 enrolled 324 participants.