BURLINGAME, Calif., Nov. 09, 2024 (GLOBE NEWSWIRE) — Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a leading clinical-stage biopharmaceutical company, has unveiled promising new data that underscore the efficacy of ciforadenant, the Company’s innovative adenosine A2A receptor antagonist, in overcoming therapeutic resistance seen in patients undergoing anti-PD1 immunotherapy for metastatic castration-resistant prostate cancer (mCRPC).
The groundbreaking data was presented today during a prominent oral session at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting by Aram Lyu, Ph.D., a distinguished postdoctoral fellow at Fred Hutch Cancer Center, University of California, San Francisco, who is also recognized as a Parker Scholar at the Parker Institute for Cancer Immunotherapy. Dr. Lyu’s compelling abstract, entitled “Identification and therapeutic target of myeloid-mediated mechanisms of immunotherapy resistance in prostate cancer,” garnered significant attention, earning a place among the Top 100 abstracts showcased at SITC.
“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,” remarked 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.”
SITC Oral Presentation Overview and Key Data
In exploring mCRPC, previous studies have documented the resistance of this cancer type to therapies employing immune checkpoint inhibitors. The research identified SPP1+ myeloid cells as significant contributors to the immunosuppressive landscape of the tumor microenvironment. The investigative team, led by Lawrence Fong, M.D., utilized single cell RNA expression profiling of tumor biopsies to ascertain the presence of these myeloid cells in different patient cohorts—those with early localized or metastatic hormone-responsive prostate cancer versus those with advanced mCRPC. The results indicated a marked increase in SPP1+ macrophage prevalence correlating with disease progression toward mCRPC.
Dr. Fong serves as the scientific director of the Immunotherapy Integrated Research Center at Fred Hutch and holds a professorship in the Translational Sciences and Therapeutics Division, additionally recognized as a Bezos Family Distinguished Scholar in Immunotherapy.
- 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
- 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 (21%) receiving combination therapy had PSA partial responses defined as PSA reductions >30%, compared to 1 of 11 (9%) receiving monotherapy
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a trailblazer in the clinical-stage biopharmaceutical realm, dedicated to innovating the application of ITK inhibition as a transformative immunotherapy approach for a diverse array of cancer types and immune-related diseases. The Company’s flagship product candidate, soquelitinib, is an investigational oral small molecule that selectively inhibits ITK, while additional clinical-stage candidates are concurrently being advanced to target various cancer indications. For further information, visit www.corvuspharma.com.
About Ciforadenant
Ciforadenant (CPI-444) represents an investigational small molecule, oral checkpoint inhibitor engineered to neutralize a tumor’s ability to thwart immune system attacks by inhibiting the binding of adenosine to immune cells located within the tumor microenvironment. Adenosine, a metabolic byproduct of ATP (adenosine tri-phosphate), is generated within the tumor’s context, where it can bind to the adenosine A2a receptor on immune cells, subsequently obstructing their immune functions. Research has established that ciforadenant can mitigate the immunosuppressive effects of myeloid cells present within tumors, with preclinical findings published in 2018 illustrating synergistic effects when used in combination with anti-PD1 and anti-CTLA4 antibodies.
Adenosine Gene Signature
The adenosine gene signature comprises a biomarker indicative of adenosine-induced immunosuppression present in tumors. This gene signature expresses specific chemokines that draw in myeloid cells, including those that are immunosuppressive, and are believed to contribute to the resistance seen against anti-PD-(L)1 therapies.
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**Interview with Dr. Aram Lyu on New Advances in Immunotherapy for Prostate Cancer**
**Editor:** Good afternoon, Dr. Lyu. Thank you for joining us today to discuss your recent findings presented at the SITC Annual Meeting. Could you start by explaining the main focus of your research on metastatic castration-resistant prostate cancer (mCRPC)?
**Dr. Lyu:** Good afternoon! Absolutely. Our research is primarily focused on understanding the mechanisms behind immunotherapy resistance in prostate cancer, especially in mCRPC. We discovered that SPP1+ myeloid cells play a significant role in creating an immunosuppressive environment within tumors. By profiling tumor biopsies, we noted a correlation—higher levels of these cells are associated with the progression of the disease, which poses a challenge when treating with immune checkpoint inhibitors like anti-PD1 therapies.
**Editor:** That sounds vital for developing more effective treatments. Can you elaborate on how ciforadenant, the adenosine A2A receptor antagonist by Corvus Pharmaceuticals, works in this context?
**Dr. Lyu:** Yes, ciforadenant targets the adenosine pathway, which is crucial for regulating immune responses in the tumor microenvironment. Our studies showed that treatment with ciforadenant reduced the infiltration of SPP1+ macrophages, thereby alleviating immunosuppression. This shift creates a more favorable environment for anti-PD1 therapies to have a more pronounced effect.
**Editor:** Interesting. You mentioned that your findings include a potential biomarker known as the Adenosine Gene Signature. How does this contribute to patient treatment?
**Dr. Lyu:** The Adenosine Gene Signature is a biomarker that reflects adenosine-induced immunosuppression in tumors. By identifying patients with increased levels of this signature, we can better select those who are more likely to respond to treatments that include ciforadenant combined with other therapies, like ipilimumab and nivolumab. This personalized approach could significantly improve treatment outcomes.
**Editor:** You highlighted some clinical trial data. Could you share any specific results that stood out from your studies?
**Dr. Lyu:** Certainly. In our Phase 1b/2 clinical trial, we saw that 21% of patients receiving ciforadenant in combination with atezolizumab had significant PSA reductions (over 30%), compared to only 9% in those receiving ciforadenant alone. This suggests that the combination therapy may enhance treatment efficacy in patients with advanced mCRPC.
**Editor:** Those results are promising and could mark a significant step forward in the treatment of prostate cancer. What do you see as the next steps for this research?
**Dr. Lyu:** The next steps involve further validating our findings in larger cohorts and possibly conducting more extensive clinical trials to confirm these results. Understanding how to optimally integrate therapies targeting the adenosine pathway with existing immunotherapies will be crucial in enhancing their effectiveness against prostate cancer and potentially other types of cancer as well.
**Editor:** Thank you, Dr. Lyu, for those insights. The work being done in this field seems pivotal for future treatment paradigms in prostate cancer. We look forward to hearing more about your ongoing research.
**Dr. Lyu:** Thank you for having me. I’m excited about the potential of these new findings and the future of immunotherapy in cancer treatment.