Last updated on August 2019

A Trial of TAK-788 (AP32788) in Non-small Cell Lung Cancer (NSCLC)


Brief description of study

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, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2), and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations, and to explore relationship between tumor and/or plasma biomarkers, and TAK-788 efficacy, safety, and/or cytochrome P450 3A (CYP3A) induction. The study will also determine the efficacy of TAK-788 in participants with locally advanced metastatic NSCLC harboring EGFR in-frame exon 20 insertion mutations who have received at least 1 prior line of therapy for locally advanced or metastatic NSCLC.

Detailed Study 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 and expansion phase, followed by an extension phase.

The objectives of the dose escalation phase are to determine the safety profile of orally administered TAK-788, including the MTD, DLTs, RP2D and 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), with or without active, measurable 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, with or without active, measurable 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, with or without active, measurable CNS metastases; and
  7. Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active, with or without active, measurable 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 341 participants.

Clinical Study Identifier: NCT02716116

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