Corvus Pharmaceuticals Reveals Ciforadenant's Role in Overcoming Immunotherapy Resistance in mCRPC

Corvus Pharmaceuticals Inc. (CRVS) has unveiled promising data regarding ciforadenant, an adenosine A2A receptor antagonist, and its potential to counteract resistance to anti-PD1 immunotherapy in treating metastatic castration-resistant prostate cancer (mCRPC). Historically, mCRPC has shown resistance to immune checkpoint inhibitors. Recent studies have identified SPP1+ myeloid cells as significant contributors to this resistance.

Research led by Dr. Lawrence Fong utilized single-cell RNA expression profiling to compare tumor biopsies from patients with early localized or metastatic hormone-responsive prostate cancer to those with mCRPC. The findings revealed a higher prevalence of SPP1+ macrophages in mCRPC patients. In a murine model, these macrophages were linked to suppressed immunity and reduced survival, with adenosine signaling through the adenosine 2A receptor playing a role.

Ciforadenant was used to inhibit this signaling, demonstrating reduced immunosuppression and increased sensitivity to anti-PD1 therapy. The treatment also decreased SPP1+ macrophage infiltration, suggesting a shift to a less immunosuppressive environment. The Adenosine Gene Signature, a biomarker of adenosine-induced immunosuppression, was elevated in SPP1+ macrophages.

The murine model results align with data from a Phase 1b/2 clinical trial involving 35 patients with advanced mCRPC. In this trial, 11 patients received ciforadenant monotherapy, while 24 received it in combination with atezolizumab. Among those receiving combination therapy, five showed PSA partial responses, defined as PSA reductions exceeding 30%, compared to one in the monotherapy group.