1053PD - A first-in-human (FIH) study of PF-04518600 (PF-8600) OX40 agonist in adult patients (pts) with select advanced malignancies

Date 10 October 2016
Event ESMO 2016 Congress
Session Immunotherapy of cancer
Topics Cancer Immunology and Immunotherapy
Presenter Adi Diab
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors A. Diab1, A. El-Khoueiry2, F.A. Eskens3, W. Ros4, J.A. Thompson5, C. Konto6, C. Bermingham6, T. Joh7, K. Liao7, B. Ganguly6, O. Hamid8
  • 1Cancer Center, MD Anderson Cancer Center, 77030 - Houston/US
  • 2Clinical Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles/US
  • 3Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam/NL
  • 4Molecular Pathology, The Netherlands Cancer Institute, Amsterdam/NL
  • 5Medical Oncology, University of Washington Seattle Cancer Care Alliance, Seattle/US
  • 6Global R&d, Rinat-Pfizer, South San Francisco/US
  • 7Global R&d, Pfizer Inc., La Jolla/US
  • 8Translational Research And Immunotherapy, The Angeles Clinic and Research Institute, Los Angeles/US

Abstract

Background

Co-stimulation of activated T cells with agonistic monoclonal antibodies (mAb) against the tumor necrosis factor receptor superfamily member OX40 offers a novel immunotherapeutic approach to cancer. OX40 engagement may co-stimulate effector T cells and deplete regulatory T cells, resulting in enhanced tumor immunity. PF-8600 is a fully human agonist IgG2 mAb that targets OX40.

Methods

A Phase 1, open label, multicenter study is ongoing to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of PF-8600 in pts with advanced melanoma, head and neck squamous cell, renal cell, or hepatocellular carcinoma. PF-8600 was administered intravenously at increasing doses (0.01 – 3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. Additional biomarker cohorts (opened at each dose level except 0.01 mg/kg) enrolled pts who consented to baseline and on-treatment tumor biopsies for immune profiling by immunohistochemistry and RNAseq.

Results

As of 09 MAR 2016, 31 pts have enrolled in the dose-escalation phase of PF-8600 study: 0.01 mg/kg (2 pts), 0.1 mg/kg (10 pts), 0.3 mg/kg (8 pts), 1.5 mg/kg (7 pts) and 3 mg/kg (4 pts). 25.8% of patients received ≥ 4 prior therapies for advanced disease. No dose limiting toxicities, no drug-related or immune related grade (G) 3-5 adverse events (AEs) were observed. Drug-related AEs (DRAEs) were all G1/2 events and occurred in 21 pts (67.7%). The most common DRAEs were fatigue (29.0%) and decreased appetite (9.7%). Out of 25 pts evaluable for response, 1 pt experienced partial response (PR, -50%, confirmed), and 15 pts experienced stable disease (SD). 11 pts remain on treatment, and 5 patients continued treatment for >13 weeks. Assessment of peripheral blood lymphocyte indicated full OX40 receptor occupancy at ≥0.3 mg/kg, and maximal memory T cell proliferation at 0.1 and 0.3 mg/kg.

Conclusions

These preliminary results demonstrate that PF-8600 is safe up to 3 mg/kg. Updated safety, antitumor activity, and biomarker data will be presented.

Clinical trial identification

NCT02315066.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Disclosure

A. Diab: Advisory board for Nektar Therapeutics. A. El-Khoueiry: Grants:NCI/NIH, CTEP, SWOG Consultant: Genentech, Bayer, Astra-Zeneca, Medimmune, Celgene, BMS, Transgene Speakers Bureau: Merrimack Contracted. Research: Pfizer,CeloNova, Novartis, AstraZeneca, BMS, Genentech, Pfizer, Astex, Daiichi Sankyo, Nektar, Exelixis, Chiltern. F.A. Eskens: Adboard for Baxalta, Merck, AMGEN. C. Konto: Pfizer's employee and shareholder. C. Bermingham: I have Pfizer stock as part of my 401K. T. Joh: I am Pfizer employee, and stock owner. K. Liao: Currently, I am employed by Pfizer Inc. and own Pfizer stock. B. Ganguly: I am a Pfizer employee and that I own Pfizer stock. O. Hamid: Consulting: Amgen, Novartis, Roche, BMS. Speaker: Amgen, BMS, Genentech, Merck, Novartis. Contracted Research: Astra Zeneca, BMS, Celldex, Genentech, Immunocore, Incyte, Merck, Merck-Serano, MedImmune, Novartis, Pfizer, Rinat, Roche. All other authors have declared no conflicts of interest.