ARIAD starts phase 1/2 trial of AP32788 in patients with non-small cell lung cancer

AP32788 targets tumors driven by EGFR or HER2 kinases and was designed to achieve selective inhibition of these kinases with exon 20 mutations.

There are currently no approved targeted treatment options available for the approximately four to nine percent of EGFR-mutated lung tumors with exon 20 insertion mutations in NSCLC patients.1 Additionally, approximately two percent of NSCLC patients2 have HER2 mutations, with the majority having exon 20 insertion mutations.

"In the preclinical data presented at the AACR meeting last month, AP32788 demonstrated the ability to inhibit all tested EGFR and HER2 mutants, including exon 20 insertion mutants," stated Tim Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD.

"We are pleased to be advancing AP32788, the next promising cancer medicine in the ARIAD pipeline, into clinical study for patients who currently have no targeted treatment options in these orphan oncology disease subsets."

Clinical Trial Design

The trial will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The initial Phase 1 dose-escalation trial segment will include patients with advanced NSCLC. Patients enrolled in this multicenter study will be refractory to standard available therapies.

The primary objective of the Phase 1 segment of the trial is to determine the safety, tolerability, pharmacokinetic profile, and recommended Phase 2 dose (RP2D) of orally administered AP32788. ARIAD expects to enroll approximately 20 to 30 patients in this portion of the trial.

The Phase 2 expansion phase of the trial will include four histologically and molecularly defined patient cohorts, including:

NSCLC patients with EGFR exon 20 activating insertions with no active, measurable central nervous system (CNS) metastases;
NSCLC patients with HER2 exon 20 activating insertions or point mutations with no active, measurable CNS metastases;
NSCLC patients with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases; and,
NSCLC with other targets against which AP32788 has shown preclinical activity (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.

The Phase 2 segment of the trial is planned to enroll approximately 80 patients and will evaluate anti-tumor activity of AP32788 in these molecularly defined patient populations.

"While there are approved TKIs for use in NSCLC patients with common EGFR activating mutations, there is a need for targeted treatment options to address the subset of patients with EGFR exon 20, HER2, and other uncommon EGFR mutations," said Robert C. Doebele, M.D., Ph.D., associate professor, division of medical oncology, University of Colorado.

"This trial will evaluate the safety, tolerability and optimal dose of AP32788, and the potential activity in NSCLC patients who currently have no targeted treatment options."

ARIAD’s Phase 1/2 clinical trial of AP32788 is expected to enroll patients at up to seven centers during the dose-escalation phase. Additional centers will be activated for enrollment of the expansion cohorts.