Corvus Pharmaceuticals announced new data highlighting the potential of ciforadenant to overcome resistance to anti-PD1 immunotherapy in metastatic castration resistant prostate cancer (mCRPC). The data was presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting.
Targeting Myeloid Cells to Enhance Immunotherapy
Previous research has indicated that mCRPC is often resistant to immune checkpoint inhibitors. This study focused on SPP1+ myeloid cells as potential mediators of this resistance. Researchers, led by Lawrence Fong, M.D., used single-cell RNA expression profiling of tumor biopsies and found that SPP1+ macrophages were more prevalent in mCRPC patients compared to those with early localized or metastatic hormone-responsive prostate cancer.
Preclinical Evidence
In a murine model, the presence of SPP1+ macrophages was associated with suppressed immunity and reduced overall survival. Further analysis revealed the involvement of adenosine signaling through the adenosine 2A receptor. Ciforadenant, an adenosine A2A receptor antagonist, was used to inhibit this signaling, resulting in:
- Reduced immunosuppression and enhanced sensitivity to anti-PD1 therapy
- Reduced SPP1+ macrophage infiltration in tumors
- Elevation of the Adenosine Gene Signature in SPP1+ macrophages
Clinical Trial Data
These findings align with data from a Phase 1b/2 clinical trial of ciforadenant in mCRPC patients. The trial included 35 patients with advanced mCRPC, with 11 receiving ciforadenant monotherapy (100 mg twice daily) and 24 receiving ciforadenant (100 mg twice daily) in combination with atezolizumab (840 mg every two weeks). Results showed that 5 of 24 patients (21%) on combination therapy experienced PSA partial responses (PSA reductions >30%), compared to 1 of 11 patients (9%) on monotherapy.
Implications for Treatment
"These studies reveal important details on the role of the adenosine pathway on the immunobiology of mCRPC, including the importance of myeloid cells and the adenosine gene signature," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "The mechanism is consistent with and builds on results from our clinical trials in renal cell cancer and prostate cancer, along with the potential for the adenosine gene signature to select patients most likely to respond. This could be an important advancement for patients with tumors that are resistant to checkpoint inhibitors, and is supportive of our ongoing clinical trial of ciforadenant in combination with ipilimumab and nivolumab in front line renal cell cancer."
