Date: 2016-05-31
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: Ariad Pharmaceuticals (USA - MA)
Product: AP32788
Action
mechanism: tyrosine kinase inhibitor. AP32788 is an investigational oral tyrosine kinase inhibitor (TKI) of activating mutations in EGFR and HER2. The molecule was designed to address the unmet need in patients with non-small cell lung cancer (NSCLC) driven by exon 20 insertion mutations in EGFR and HER2, and is ARIAD's fourth internally discovered oncology candidate to advance into clinical development.
Disease: non-small cell lung cancer (NSCLC) with specific mutations in EGFR or HER2
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The purpose of this phase 1/2 study is to evaluate the safety, pharmacokinetics, and anti-tumor activity of oral AP32788 in patients with non-small cell lung cancer (NSCLC). The trial will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The goal of the dose escalation phase is to determine the safety profile of orally administered AP32788, including the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), recommended phased 2 dose (RP2D) and pharmacokinetic profile. Once the RP2D is established, the expansion phase will assess the preliminary anti-tumor activity of AP32788 in 4 histologically and molecularly defined NSCLC cohorts. Approximately 105 patients will be enrolled. 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. (NCT02716116)
Latest
news: * On May 31, 2016, Ariad Pharmaceuticals announced initiation of the Phase 1/2 clinical trial of AP32788 designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in EGFR or HER2. 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. Additionally, approximately two percent of NSCLC patients have HER2 mutations, with the majority having exon 20 insertion mutations. 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 trial 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. * On February 1, 2016, Ariad Pharmaceuticals announced that the FDA has completed its review of the Company's Investigational New Drug (IND) application for AP32788, a tyrosine kinase inhibitor (TKI) designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in EGFR or HER2. ARIAD anticipates initiation of its Phase 1/2 clinical trial of AP32788 in patients with NSCLC in the second quarter of 2016.
