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Published on: December 21, 2019
A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207
Paul Wheatley-Price1, Quincy Chu2, Maria Bonomi3
1Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Abstract:
There is no approved second-line systemic therapy option for malignant pleural mesothelioma (MPM), but targeting angiogenesis is an area of investigation. PF-03446962 is a fully human antibody against activin receptor-like kinase 1, which is commonly expressed in tumor vasculature. We performed a multicenter, open label, single-arm, two-stage phase II study of PF-03446962 in patients with MPM and progressive disease after platinum-based chemotherapy. In total, 17 patients were enrolled, but no partial or complete responses were observed. The trial did not meet the prespecified response criterion for moving to the second stage. There were only three grade 3 (G3) or higher nonhematological toxicities observed (G3 hypertension [n=2] and G3 fatigue [n=1]) and just one episode of G3 lymphopenia. In conclusion, PF-03446962, despite being generally well tolerated, failed to demonstrate efficacy in the treatment of advanced MPM as a single agent. There are no plans for further investigation of this agent in MPM.
Insights
This study found that PF-03446962, an investigational drug targeting angiogenesis, did not show efficacy as a second-line treatment for malignant pleural mesothelioma (MPM). The drug was well-tolerated but failed to meet response criteria in patients with advanced MPM.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Malignant pleural mesothelioma (MPM) lacks approved second-line systemic therapies.
- Targeting angiogenesis, a process crucial for tumor growth, is a potential therapeutic strategy.
- Activin receptor-like kinase 1 (ALK1) is expressed in tumor vasculature and is a target for PF-03446962.
Purpose of the Study:
- To evaluate the efficacy and safety of PF-03446962 as a second-line treatment for patients with advanced malignant pleural mesothelioma (MPM).
- To assess the response rate of PF-03446962 in patients with MPM progressing after platinum-based chemotherapy.
Main Methods:
- A multicenter, open-label, single-arm, two-stage phase II study was conducted.
- Seventeen patients with advanced MPM and disease progression after platinum-based chemotherapy were enrolled.
- Patients received PF-03446962 as a single agent.
Main Results:
- No partial or complete responses were observed in the 17 enrolled patients.
- The study did not meet the prespecified response criterion to advance to the second stage.
- PF-03446962 was generally well-tolerated, with limited grade 3 or higher nonhematological toxicities (hypertension, fatigue) and lymphopenia.
Conclusions:
- PF-03446962 demonstrated a lack of efficacy as a single agent in treating advanced malignant pleural mesothelioma.
- Despite a favorable safety profile, the investigational drug failed to meet primary efficacy endpoints.
- Further investigation of PF-03446962 for MPM is not planned based on these findings.
