Corvus Pharmaceuticals Presents Updated Clinical Data Supporting and Refining the Adenosine Gene Signature’s Ability to Identify Patients Likely to Respond to Treatment with Ciforadenant
Elucidation of CD68 as a Downstream Target of Adenosine Refines Adenosine Gene Signature into a Practical Pathology Test Provides Opportunity to Further Enrich Patient Selection for Responders
Data Includes Additional Patients with Advanced Refractory Renal Cell Cancer, Supporting Earlier Results Published in Cancer Discovery in January
Data Presented at the ASCO20 Virtual Scientific Program
“We are pleased that the utility of the Adenosine Gene Signature as a biomarker for ciforadenant treatment has been supported in a larger number of patients,” said
The updated data covers 51 RCC patients that were treated with ciforadenant monotherapy or in combination with Genentech’s Tecentriq® (atezolizumab), an anti-PD-L1 antibody, and whose tumors were biopsied to test with the AdenoSig. The data were made available today in an on-demand, electronic poster format for registered participants of the ASCO20 Virtual Scientific Program, which is taking place from
- 31 patients (30 evaluable) were positive for the AdenoSig and 20 patients were negative. Patients had a median of three prior therapies, including 86% that failed a prior anti PD-(L)1 therapy.
- In the AdenoSig positive group, there were five partial responses (PR, RECIST) for an ORR of 17% and six additional patients that had tumor regression not meeting the criteria for a PR.
- In the AdenoSig negative group, there were no PRs and no patients with tumor regression.
- In the AdenoSig positive group, the progression free survival (PFS) curve plateaued at 23% at 40 weeks, compared to declining to 0% in the AdenoSig negative group.
In addition, the enrollment of new patients in the study was intended to support the study and refinement of the AdenoSig. As part of this work, Corvus investigators demonstrated that CD68 positive (CD68+) myeloid cells, which are known to be myeloid derived suppressor cells, are the downstream target of adenosine present in the tumor microenvironment. Immunohistochemistry (IHC) testing showed that an increase of CD68+ myeloid cells in a tumor further enriched the AdenoSig identification of responders to treatment with ciforadenant. This work indicates that the single CD68+ IHC test could potentially be utilized to enrich patient selection for responding patients and as a substitute for the AdenoSig biomarker previously utilized by Corvus. The key data related to CD68 presented in the poster include:
- CD68 analysis was available for 53 patients, including 15 CD68 positive (CD68+) and 38 CD68 negative (CD68-) patients.
- All but one patient in the study with a PR were in the CD68+ group.
- The ORR in the CD68+ group was 26.7% (4 of 15), compared to an ORR of 2.6% (1 of 38) in the CD68- group.
- Treatment with ciforadenant was associated with a reduction of infiltrating CD68+ cells in pre-treatment compared to on-treatment tumor biopsies (paired to individual patients), supporting the biologic effects of ciforadenant and the potential predictive utility of CD68 to identify RCC patients most likely to respond to treatment with ciforadenant.
About Corvus Pharmaceuticals
Ciforadenant (CPI-444) is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.
Adenosine Gene Signature and CD68+ Myeloid Cells
The adenosine gene signature is a biomarker that reflects adenosine induced immunosuppression in the tumor. These genes express chemokines that recruit myeloid cells including immunosuppressive tumor associated CD68+ myeloid cells, which are thought to mediate resistance to anti-PD-(L)1 treatment. To date, in our clinical trial of renal cell cancer, this biomarker has been associated with a higher rate of response to ciforadenant. CD68+ cells can be enumerated using standard immunohistochemical techniques that are routinely available in pathology laboratories.
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of ciforadenant, the Company’s ability to identify and utilize the adenosine gene signature or the CD68+ gene for purposes of its clinical trials, including the Company’s Phase 1b/2 clinical trial of ciforadenant . All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the quarter ended
Chief Financial Officer
Source: Corvus Pharmaceuticals, Inc.