Date: 2014-05-31
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Aveo Oncology (USA - MA)
Product: AV-203
Action
mechanism: AV-203 is a clinical-stage ErbB3 (HER3) inhibitory antibody candidate designed to inhibit both ligand-dependent and ligand-independent ErbB3 signaling. ErbB3 is a receptor that is typically expressed in many human cancers, and AV-203 has demonstrated preclinical activity in a number of different tumor models including breast, head and neck, lung, ovarian and pancreatic cancers. AVEO has successfully completed a Phase 1 safety study showing no dose limiting toxicities at maximum dose of 20mg/kg and CLIA (Clinical Laboratory Improvements Amendment) validation has been completed for a biomarker for potential patient selection.
Disease: metastatic or advanced solid tumors
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 31, 2014, AVEO Oncology announced the presentation of results from a first-in-human Phase 1 study of AV-203, AVEO’s ErbB3 (HER3) inhibitory antibody candidate. Among the results, the study established a recommended Phase 2 dose of AV-203, demonstrated good tolerability and promising early signs of activity, and reached the maximum planned dose of AV-203 monotherapy. The results were presented in a poster, entitled “First-in-human Phase 1 dose-escalation study of AV-203, a monoclonal antibody against ErbB3 in patients with metastatic or advanced solid tumors” (Abstract #11113, Poster #395, S Hall A2), at the Tumor Biology General Poster Session of the American Society of Clinical Oncology 2014 Annual Meeting, taking place May 30 - June 3, 2014, in Chicago.
A total of 22 patients were evaluated in the Phase 1, open-label, dose-escalation study. Objectives included safety, tolerability, dose limiting toxicities (DLT), maximum tolerated dose and/or recommended phase 2 dose in patients with advanced solid tumors. Evaluation of NRG-1 as a predictive biomarker was an exploratory objective. Patients received 2, 5, 9, 14, or 20 mg/kg of AV-203 intravenously once every 2 weeks (2 times per 28 day cycle). AV-203 was found to be generally safe and well-tolerated, with diarrhea and decreased appetite as the most common treatment-emergent and treatment-related adverse events (all grade). Across all doses of AV-203, there was a single DLT that occurred in an elderly patient at the lowest dose cohort (inability to tolerate study drug). The recommended Phase 2 dose was established at 20mg/kg intravenously every 2 weeks. No anti-drug antibodies were detected, and pharmacokinetic results indicated a dose-proportional increase in levels of AV-203.
Among 22 evaluable patients, stable disease was the best response for 8 patients, including a partial response lasting 6 cycles and a long-term stable disease lasting at least 22 cycles (>98 weeks), resulting in a disease control rate of 36%. Neuregulin-1 (NRG-1, also known as heregulin or HRG) status, which AVEO’s preclinical studies suggest is predictive of AV-203 anti-tumor activity, was analyzed via RT-PCR. Of 14 subjects analyzed for NRG-1 expression, two patients were NRG-1 positive, one of whom, a patient with squamous non–small cell lung cancer, achieved a partial response. CLIA (Clinical Laboratory Improvements Amendment) validation is complete for an NRG-1 biomarker assay for potential use in patient selection in future clinical trials. In March 2014, AVEO announced that it completed negotiations to reacquire worldwide rights for AV-203 from ex-US licensor Biogen Idec, a company which had previously announced plans to shift its therapeutic focus away from oncology.
