809O - Immune correlates and long term follow up of a phase Ia study of MPDL3280A, an engineered PD-L1 antibody, in patients with metastatic renal cell ca...

Date 29 September 2014
Event ESMO 2014
Session Genitourinary tumours, non prostate immunotherapy
Topics Renal Cell Cancer
Cancer Immunology and Immunotherapy
Translational Research
Presenter David McDermott
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors D.F. McDermott1, M. Sznol2, J.A. Sosman3, J. Soria4, M.S. Gordon5, O. Hamid6, J. Delord7, M. Fasso8, Y. Wang9, J. Bruey10, G. Fine11, T.B. Powles12
  • 1Division Of Hematology/oncology, Beth Israel Deaconess Medical Center, 02215 - Boston/US
  • 2Section Of Medicine Oncology, Yale Cancer Center, New Haven/US
  • 3Haematology/ Oncology, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 4Dept. Of Medicine, Institut Gustave Roussy, Villejuif CEDEX/FR
  • 5Pinnacle Oncology Hematology, Oncology Research Associates, Scottsdale/US
  • 6Melanoma Center, The Angeles Clinic and Research Institute, Los Angeles/US
  • 7Oncologie, Institut Claudius Regaud, Toulouse/FR
  • 8Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 9Pdb Biostatistics, Genentech, Inc., South San Francisco/US
  • 10Clinical Research, Genentech, Inc., South San Francisco/US
  • 11Biooncology, Genentech, South San Francisco/US
  • 12Barts Cancer Institute, Queen Mary University of London, London/GB

Abstract

Aim

PD-L1, which can mediate cancer immune evasion, is broadly expressed in RCC. As RCC can respond to immune-based therapy, blocking PD-L1 represents a strategy to restore tumor-specific T-cell immunity. MPDL3280A, a human mAb containing an engineered Fc-domain, targets PD-L1 to prevent binding to its receptors PD-1 and B7.1 on activated T cells. Interim results showed that MPDL3280A had a manageable safety profile and clinical activity in advanced NSCLC, melanoma and mRCC pts. Here, we report long term follow up and correlative data for the RCC cohort.

Methods

mRCC pts were enrolled in a Ph I expansion study. All pts who received MPDL3280A IV q3w at doses of 3-20 mg/kg were evaluable for safety. Pts were treated for ≤ 1 y. Response was assessed by RECIST v1.1. PD-L1 IHC was centrally assessed in tumor biopsies.

Results

As of Jan 1, 2014, among 69 mRCC pts evaluable for safety, median age was 61 y and all were ECOG PS 0-1 (48% PS 1). 94% of pts had prior nephrectomy and 87% received prior systemic therapy, including cytokines (39%), VEGF-inhibition (64%) and mTOR inhibitors (26%). Pts received MPDL3280A for a median duration of 7.7 m (0.7-24.3 m). 80% of pts had a treatment-related AE; however, the frequency of G3 related events was 16%, including anemia, dehydration, fatigue and hypophosphatemia (3% each). No related G4 AEs or deaths occurred. Clinical activity was evaluated in 58 pts with clear cell histology dosed prior to Jul 1, 2013; 51 pts (88%) had an evaluable baseline PD-L1 IHC status. The ORR was 14% (8/58 PRs, 95% CI: 6, 25) and the median duration of response was 54 wks (2.7+ to 68.1+ wks). The 24-wk PFS rate was 53% (95% CI: 40, 66). An association was seen between PD-L1 intensity and response to MPDL3280A. Finally, antitumor activity that included immune-related responses was observed in non-clear cell histology pts (n = 10). Updated data including biomarkers will be presented.

Conclusions

MPDL3280A was well tolerated, with no treatment-related deaths. Evidence of increased activity was observed in pts with elevated PD-L1. Durable responses and prolonged SD were observed in mRCC pts, warranting further study.

Disclosure

D.F. McDermott: has participated in advisory boards for Genentech, BMS and Merck; M. Sznol: has consulted for Immune Design, Merus, Lion Biotechnologies, Kyowa-Kirin, Aztra-Zeneca-Medimmune, BMS, Amgen, Medimmune, Genentech, Symphogen, Nektar, and Anaeropharma; J. Soria: has received honoraria from Genentech and Roche; M.S. Gordon: has served in an advisory/consultant role and has received research funding from Roche/Genentech; O. Hamid: has been a speaker and consultant for Genentech, and research funding has been provided by Genentech; M. Fasso, Y. Wang, J. Bruey and G. Fine: is employed by Genentech. All other authors have declared no conflicts of interest.