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 Cytotoxic agents
Mesothelioma
Therapy
Biological therapy
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.