1105TiP - Phase 1/1b multicenter trial of the adenosine A2a receptor antagonist (A2aR) CPI-444 as single agent and in combination with atezolizumab (ATZ) in...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Therapy
Presenter Amita Patnaik
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors A. Patnaik1, J. Powderly2, J. Luke3, R. Miller4, G. Laport4
  • 1Medical Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 2Medical Oncology, Carolina BioOncology Institute, 28078 - Huntersville/US
  • 3Section Of Hematology/oncology, The University of Chicago Medical Centre, Chicago/US
  • 4Clinical Development, Corvus Pharmaceuticals, 94010 - Burlingame/US

Abstract

Background

Adenosine is an extracellular signaling molecule that increases in response to acute tissue injury/inflammation to restore tissue homeostasis. Elevated levels of adenosine are produced in the tumor microenvironment and signaling through A2aR on immune cells leads to immunosuppression, promoting tumor growth. CPI-444 is an oral A2aR antagonist that has been evaluated in phase 1 and 2 clinical trials outside the oncology setting. CPI-444 binds to A2aR with a Ki of 3.5 nM and > 50 fold selectivity over other adenosine receptor subtypes. Preclinical studies with various mouse tumor models demonstrate efficacy of CPI-444 as a single agent(SA) and in combination with anti-PD1/PDL1 antibodies.

Trial design

We have initiated a phase 1/1b multicenter, open label trial to evaluate CPI-444 as a SA and in combination with ATZ(anti-PDL1), in pts with advanced cancers. The objectives are 1)evaluate the safety and tolerability of multiple doses of CPI-444 2) identify a recommended dose and schedule for further study and 3) evaluate efficacy. Eligibility criteria: 1)histology: non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, bladder cancer, head and neck cancer and MSI colorectal cancer and 2) 1 but not more than 5 prior therapies. This phase 1/1b adaptive design is composed of 2 steps with multiple expansion cohorts within Step 2 based on a 3-stage expansion design. Step 1 is a dose selection step with 4 cohorts (3 SA cohorts with CPI-444 at various dosing schedules and 1 cohort combined with ATZ). After Step 1, the optimal dose SA cohort of CPI-444 determined by safety and other biomarkers and the optimal dose from the combination cohort will proceed to Step 2. Step 2 has 10 multiple expansion cohorts: 5 cohorts (stratified by disease)will receive CPI-444 as a SA and 5 cohorts will receive the combination. The total sample size is up to 534 pts. This trial is accruing in N America and will expand to Australia and Europe.

Clinical trial identification

NCT02655822 Release date: January 08, 2016

Legal entity responsible for the study

Corvus Pharmaceuticals

Funding

Corvus Pharmaceuticals

Disclosure

A. Patnaik: Research support to institution: Corvus Pharmaceuticals. J. Powderly: Clinical Research Funding: Bristol Myers Squibb, Genentech, Corvus, AstraZeneca, Incyte, Macrogenics, EMD Serono, Sequonom Stock Equity: Bluebird Bio, Kite PHarma ZioPHarm Oncology, Juno Therapeutics, Lion BioTechnologies. J. Luke: Ad board: Amgen, Array Research support to institution: Novartis, MedImmune, Bristol-Myers Squibb, Pharmacyclics, Merck, BBI Therapeutics, Five Prime Therapeutics, Genentech, Corvus Pharmaceuticals, Delcath, Abbvie, Celldex, EMD Serono, Incyte. R. Miller: Employee and stockholder of Corvus Pharmaceuticals. G. Laport: Employee and stockholder of company.