A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207

Our plain-English summary of A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207, by P. Wheatley-Price, Q. Chu, M. Bonomi, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: P. Wheatley-Price, Q. Chu, M. Bonomi, J. Seely, A. Gupta, G. Goss, J. Hilton, R. Feld, C.W. Lee, J.R. Goffin, A. Maksymiuk, N. Murray, L. Hagerman, P.A. Bradbury
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(11):2018-2021
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This drug trial involved people already diagnosed with malignant pleural mesothelioma. It did not study asbestos exposure. The Canadian Cancer Trials Group ran a nonrandomized, open-label phase II study at seven Canadian centers. It tested PF-03446962, an antibody against ALK-1, a receptor found in tumor blood vessels. Patients whose disease had progressed after one line of platinum-based doublet chemotherapy received 10 mg/kg intravenously every 14 days. Seventeen patients enrolled between April 2012 and January 2014. Among the 15 who could be assessed, none had a partial or complete response (response rate 0%). Two had stable disease lasting 2.7 and 3.6 months. With fewer than two responses, the trial did not proceed to its planned second stage. Nausea was the most frequent non-laboratory side effect (35%). On laboratory tests, anemia and low blood albumin were each recorded in 12 of 17 patients (71%). Grade 3 events were two cases of high blood pressure, one of fatigue, one of lymphopenia and two of low blood albumin. There were no grade 4 or 5 treatment-related events. The authors concluded the drug was well tolerated but did not show evidence of effectiveness as second-line treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nonrandomized, open-label, single-arm, two-stage phase II drug trial (CCTG IND.207) at seven centers
• Who was studied: 17 patients with advanced malignant pleural mesothelioma of any histologic type, enrolled in Canada from April 2012 to January 2014, whose disease had progressed after one line of platinum-based doublet chemotherapy. 71% were male, median age 68 years (range 48 to 79), and 71% had the epithelioid subtype.
• Exposure: Not an asbestos exposure study. The treatment studied was PF-03446962, a fully human anti-ALK-1 antibody, given as a 1-hour intravenous infusion of 10 mg/kg on day 1 of each 14-day cycle until progression, unacceptable toxicity or withdrawal of consent.
• Main results:
  • Among the 15 patients evaluable for response, there were no partial or complete responses, so the overall response rate was 0%.
  • Stable disease occurred in two patients, lasting 2.7 and 3.6 months.
  • Because fewer than two responses were observed, the trial did not proceed to stage II.
  • Among non-laboratory treatment-related adverse events, the most frequent were nausea (35%), headache (24%), and proteinuria, vomiting and hypertension (all 18%). Most adverse events were grade 1 or 2.
  • Among laboratory treatment-related adverse events in Table 1, anemia and hypoalbuminemia each occurred in 12 patients (71%), lymphopenia in 9 (53%), increased creatinine in 8 (47%) and hyperglycemia in 7 (41%).
  • Grade 3 non-laboratory events were two instances of hypertension and one of fatigue. There were no grade 4 or 5 treatment-related adverse events.
  • Grade 3 laboratory events were one episode of lymphopenia and two of hypoalbuminemia, with no other grade 3 or 4 laboratory events.
  • No patient needed a dose reduction. There were three dose delays. Treatment was stopped for objective progression in 14 patients.
• The authors' conclusion: The authors concluded that PF-03446962 was well tolerated but did not show evidence of efficacy in second-line treatment of malignant pleural mesothelioma.
• Limitations the authors state:
  • The planned correlative investigation of ALK-1 expression was not performed because of the lack of efficacy.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Systemic Therapy, Angiogenesis, Chemotherapy.

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