Corvus Pharmaceuticals Establishes New Promising Data For Ciforadenant In Tackling Prostate Cancer’s Immunotherapy Resistance

Corvus Pharmaceuticals, Inc., a biopharmaceutical company in the clinical trial phase, released new findings on the potential of its adenosine A2A receptor antagonist, ciforadenant, to help counter resistance to anti-PD1 immunotherapy in treating metastatic castration-resistant prostate cancer (mCRPC). 

These findings were presented in an oral session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) by Dr. Aram Lyu, a postdoctoral researcher at Fred Hutch Cancer Center, associated with both the University of California, San Francisco and the Parker Institute for Cancer Immunotherapy. Dr Lyu's work, titled "Identification and therapeutic target of myeloid-mediated mechanisms of immunotherapy resistance in prostate cancer," was recognised as one of the SITC's Top 100 abstracts.

Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus, said, “These studies reveal essential details on the role of the adenosine pathway on the immunobiology of mCRPC, including the importance of myeloid cells and the adenosine gene signature. 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.”

Summary of SITC Presentation and Key Findings 

Research has shown that mCRPC is typically resistant to immune checkpoint inhibitors. Tumour-associated macrophages have long been associated with immunosuppressive effects in the tumor microenvironment, but this study pinpointed SPP1+ myeloid cells as a critical factor in resistance to immunotherapy. 

Under the guidance of Dr Lawrence Fong, scientific director at Fred Hutch’s Immunotherapy Integrated Research Center, the research team analyzed single-cell RNA expression data from prostate cancer tumor biopsies, comparing patients with early-stage or hormone-responsive prostate cancer to those with mCRPC. They discovered a higher presence of SPP1+ macrophages as cancer advances to mCRPC.

To explore these findings, the researchers developed a mouse model showing that SPP1+ macrophages suppress immune response in prostate cancer, reducing survival rates. Further genetic analysis revealed that adenosine signaling, mainly through the A2A receptor, played a significant role in this immune suppression. They then tested ciforadenant in this model to block the adenosine pathway, yielding promising results such as:

- Reduced immunosuppression and increased tumor sensitivity to anti-PD1 therapy

- Decreased levels of SPP1+ macrophages within tumors, shifting the tumor environment towards a less immunosuppressive state

- An increase in the Adenosine Gene Signature in SPP1+ macrophages, a biomarker indicating adenosine-driven immunosuppression

- These model results were consistent with early data from a Phase 1b/2 trial in patients with advanced mCRPC. This study included 35 patients, with 11 receiving ciforadenant alone (100 mg twice daily) and 24 receiving a combination of ciforadenant (100 mg twice daily) with atezolizumab (840 mg every two weeks). Among those on combination therapy, 5 of 24 (21%) achieved partial PSA responses (reductions over 30%), while 1 of 11 (9%) receiving only ciforadenant had similar results.