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.