Corvus Unveils Data On Ciforadenant's Potential To Overcome Immunotherapy Resistance In MCRPC

Corvus Pharmaceuticals

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(RTTNews) - Corvus Pharmaceuticals Inc. (CRVS) announced new data highlighting the potential of ciforadenant, the Company's adenosine A2A receptor antagonist, to overcome resistance to anti-PD1 immunotherapy in the treatment of metastatic castration resistant prostate cancer or mCRPC.

The company noted that previous studies have shown that mCRPC is resistant to therapy with immune checkpoint inhibitors. While tumor associated macrophages are known to contribute to immunosuppression with the tumor microenvironment, this study identified SPP1+ myeloid cells as a potential critical mediator of resistance to immunotherapy.

The team led by Lawrence Fong, M.D. used single cell RNA expression profiling of tumor biopsies to measure levels of these cells in patients with early localized or metastatic hormone responsive prostate cancer compared to patients with mCRPC. The results showed that SPP1+ macrophages were more prevalent as cancer progresses to mCRPC patients, the company said.

The company noted that researchers created a murine model that confirmed that SPP1+ macrophages were associated with suppressed immunity to prostate cancer and shortened overall survival. Further analysis of the related genetic pathways revealed involvement of adenosine signaling through the adenosine 2A receptor. The researchers utilized ciforadenant to inhibit adenosine signaling in this model and the key findings demonstrating its potential to overcome this resistance to immunotherapy include: Ciforadenant treatment associated with reduced immunosuppression and enhanced sensitivity to anti-PD1 therapy in the model; Ciforadenant treatment associated with reduced SPP1+ macrophage infiltration in the tumors, supporting a shift to a less immunosuppressive myeloid environment; The Adenosine Gene Signature, a biomarker that reflects adenosine induced immunosuppression in the tumor, was elevated in SPP1+ macrophages.

According to the company, results from the model were consistent with data from the Phase 1b/2 clinical trial of ciforadenant in patients with mCRPC, which included data from 35 patients with advanced mCRPC, including 11 who received ciforadenant as a monotherapy (100 mg twice daily) and 24 that received ciforadenant (100 mg twice daily) in combination with atezolizumab (840 mg delivered intravenously every two weeks). 5 of 24 receiving combination therapy had PSA partial responses defined as PSA reductions more than 30%, compared to 1 of 11 receiving monotherapy.

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