1522PD - A multi-center phase II clinical trial of the chimeric anti-mesothelin monoclonal antibody amatuximab in combination with chemotherapy for frontline...

Date 29 September 2012
Event ESMO Congress 2012
Session NSCLC - Immunotherapy, SCLC and Mesothelioma
Topics Anti-Cancer Agents & Biologic Therapy
Mesothelioma
Presenter Martin Reck
Authors M. Reck1, R. Hassan2, T. Jahan3, H. Kindler4, L. Bazhenova5, P. Fatato6, J.W. Heyburn6, J. Parno6, J.D. Maltzman6, B. Wallin6
  • 1Department Of Thoracic Oncology, Lungen Clinic Grosshandorf, 22927 - Grosshansdorf/DE
  • 2Laboratory Of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland/US
  • 3Division Of Hematology/oncology, University of California - San Francisco, San Francisco/US
  • 4University Of Chicago, Division of Oncology, Chicago/US
  • 5Health Sciences, UCSD Moores Cancer Center, La Jolla/US
  • 6Oncology, Morphotek, Exton/US

Abstract

Background

Amatuximab (MORAb-009) is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in malignant mesothelioma (MPM). Based on amatuximab results in a phase I clinical trial and pre-clinical studies showing synergy in combination with chemotherapy, a single arm phase II study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in MPM patients (Pts).

Methods

Eligibility criteria: unresectable epithelial or biphasic MPM, no prior chemotherapy and Karnofsky Performance Status (KPS) >70%. Pts received amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m2 and C 75 mg/m2 (PC) given on day 1 of each 21-day cycle for 6 cycles. Pts with objective response or stable disease received amatuximab monotherapy until disease progression. Primary endpoint: progression-free survival (PFS) at 6 months (mo). Secondary endpoints: overall survival (OS), objective response rate (ORR), pulmonary function (PFT), and safety of amatuximab with PC.

Results

89 pts with unresectable MPM were enrolled at 26 sites. Pt characteristics: median age 67 yrs (range 46-80); 78% male; 70% with KPS >90%; 89% epithelial MPM, 11% biphasic MPM; 88% had stage III/IV disease. Median PC-amatuximab cycles: 5 (range 1-6). 56 (63%) pts subsequently received single agent amatuximab. In addition to expected toxicities from PC, hypersensitivity reactions (12.4%; Grade 3/4 = 5%) from amatuximab were noted. By independent radiological review, 30 pts (39%) had a partial response and 39 (51%) had stable disease. PFS at 6 mo: 52% (95% CI: 39.5-63.5). Median PFS = 6.1 mo (95% CI: 5.4-6.5). Median OS = 14.8 mo (95% CI: 12.4 – 19.2). 29 pts are alive and 5 pts are still receiving maintenance amatuximab. The mean Forced Vital Capacity (FVC) change from baseline was 132ml. The proportion of pts with an FVC improvement of > 400ml was 23%.

Conclusions

Amatuximab in combination with PC was generally well-tolerated in this study in MPM pts with a disease control rate of 90%. The median OS of 14.8 months compares favorably with historical controls.

Disclosure

M. Reck: Advisory Board (compensated): Hoffmann-La Roche, Lilly, AstraZeneca, Pfizer, Daiichi-Sankyo, BMS. Honoraria for lectures: Hoffmann-La Roche, Lilly, AstraZeneca, Daiichi-Sankyo

T. Jahan: research funding from Genentech, Lilly and Pfizer

H.L. Kindler: research funding for morphotek

P. Fatato: Employee of Morphotek

J.W. Heyburn: Employee of Morphotek

J. Parno: Employee of Morphotek

J.D. Maltzman: Employee of Morphotek

B. Wallin: Employee of Morphotek

All other authors have declared no conflicts of interest.