Corvus Pharmaceuticals Announces New Data Highlighting Potential of Ciforadenant to Overcome Immunotherapy Resistance in Metastatic Castration Resistant Prostate Cancer
Corvus Pharmaceuticals (NASDAQ: CRVS) presented new data at SITC's 39th Annual Meeting showing ciforadenant's potential to overcome resistance to anti-PD1 immunotherapy in metastatic castration resistant prostate cancer (mCRPC). The research, selected as a Top 100 abstract, identified SPP1+ myeloid cells as critical mediators of immunotherapy resistance. Clinical trial results showed that when ciforadenant was combined with atezolizumab, 5 of 24 patients (21%) achieved PSA partial responses, compared to 1 of 11 (9%) with ciforadenant monotherapy. The study demonstrated that ciforadenant treatment reduced immunosuppression and enhanced sensitivity to anti-PD1 therapy.
Corvus Pharmaceuticals (NASDAQ: CRVS) ha presentato nuovi dati al 39° Congresso Annuale della SITC, evidenziando il potenziale del ciforadenant nel superare la resistenza all'immunoterapia anti-PD1 nel carcinoma prostatico resistente alla castrazione metastatica (mCRPC). La ricerca, selezionata come uno dei migliori 100 abstract, ha identificato le cellule mieloidi SPP1+ come mediatori critici della resistenza all'immunoterapia. I risultati degli studi clinici hanno mostrato che quando il ciforadenant è stato combinato con l'atezolizumab, 5 dei 24 pazienti (21%) hanno raggiunto risposte parziali del PSA, rispetto a 1 degli 11 (9%) trattati con monoterapia di ciforadenant. Lo studio ha dimostrato che il trattamento con ciforadenant ha ridotto l'immunosoppressione e ha aumentato la sensibilità alla terapia anti-PD1.
Corvus Pharmaceuticals (NASDAQ: CRVS) presentó nuevos datos en la 39ª Reunión Anual de la SITC, mostrando el potencial del ciforadenant para superar la resistencia a la inmunoterapia anti-PD1 en el cáncer de próstata resistente a la castración metastásico (mCRPC). La investigación, seleccionada como uno de los Top 100 resúmenes, identificó las células mieloides SPP1+ como mediadores críticos de la resistencia a la inmunoterapia. Los resultados del ensayo clínico mostraron que cuando el ciforadenant se combinó con atezolizumab, 5 de 24 pacientes (21%) lograron respuestas parciales de PSA, en comparación con 1 de 11 (9%) con monoterapia de ciforadenant. El estudio demostró que el tratamiento con ciforadenant redujo la inmunosupresión y mejoró la sensibilidad a la terapia anti-PD1.
코르부스 제약 (NASDAQ: CRVS)은 SITC 제39회 연례 회의에서 전이성 거세 저항성 전립선암 (mCRPC)에서 항-PD1 면역 요법에 대한 저항성을 극복할 수 있는 ciforadenant의 잠재성을 보여주는 새로운 데이터를 발표했습니다. 선정된 연구는 면역 요법 저항의 중요한 매개체로 SPP1+ 미세구슬 세포를 확인했습니다. 임상 시험 결과에 따르면 ciforadenant와 atezolizumab을 조합했을 때 24명의 환자 중 5명(21%)이 PSA 부분 반응을 기록한 반면, ciforadenant 단독 요법으로는 11명 중 1명(9%)만이 반응을 보였습니다. 이 연구는 ciforadenant 치료가 면역 억제를 줄이고 항-PD1 요법에 대한 감수성을 향상시켰음을 입증했습니다.
Corvus Pharmaceuticals (NASDAQ: CRVS) a présenté de nouvelles données lors de la 39e réunion annuelle de la SITC, montrant le potentiel du ciforadenant pour surmonter la résistance à l'immunothérapie anti-PD1 dans le cancer de la prostate résistant à la castration métastatique (mCRPC). La recherche, sélectionnée parmi les 100 meilleures abstracts, a identifié les cellules myéloïdes SPP1+ comme des médiateurs critiques de la résistance à l'immunothérapie. Les résultats des essais cliniques ont montré que lorsque le ciforadenant était combiné à l'atezolizumab, 5 des 24 patients (21%) ont obtenu des réponses partielles au PSA, contre 1 des 11 (9%) avec monothérapie au ciforadenant. L'étude a démontré que le traitement par ciforadenant réduisait l'immunosuppression et augmentait la sensibilité à la thérapie anti-PD1.
Corvus Pharmaceuticals (NASDAQ: CRVS) hat auf dem 39. Jahreskongress der SITC neue Daten vorgestellt, die das Potenzial von Ciforadenant zeigen, die Resistenz gegen die Anti-PD1-Immuntherapie beim metastasierten kastrationsresistenten Prostatakrebs (mCRPC) zu überwinden. Die als Top 100 Abstract ausgewählte Forschung identifizierte SPP1+ myeloische Zellen als kritische Mediatoren der Immuntherapieresistenz. Die Ergebnisse der klinischen Studien zeigten, dass 5 von 24 Patienten (21%) eine partielle PSA-Ansprechrate erzielten, wenn Ciforadenant mit Atezolizumab kombiniert wurde, im Vergleich zu 1 von 11 (9%) mit der Monotherapie von Ciforadenant. Die Studie hat gezeigt, dass die Behandlung mit Ciforadenant die Immunsuppression reduzierte und die Empfindlichkeit gegenüber der Anti-PD1-Therapie erhöhte.
- Clinical trial showed 21% response rate in combination therapy vs 9% in monotherapy
- Research selected as Top 100 abstract at SITC Annual Meeting
- Demonstrated potential to overcome immunotherapy resistance in mCRPC
- Low overall response rates in both monotherapy (9%) and combination therapy (21%)
- Study to small patient sample size (35 patients total)
Insights
The new preclinical data for ciforadenant in metastatic castration resistant prostate cancer (mCRPC) shows promising potential to overcome immunotherapy resistance. Key findings demonstrate that SPP1+ macrophages play a important role in immunotherapy resistance and ciforadenant effectively reduces their presence in tumors.
The clinical trial results, while early, are encouraging with a
The mechanism of action through adenosine A2A receptor antagonism provides a clear scientific rationale, supported by both preclinical and clinical data. This dual validation strengthens the development pathway for ciforadenant in this difficult-to-treat cancer type.
Data presented in an oral session at the Society for Immunotherapy of Cancer 39th Annual Meeting, where it was selected as a top 100 abstract
BURLINGAME, Calif., Nov. 09, 2024 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today 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 (mCRPC).
The data were presented today in an oral session at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting by Aram Lyu, Ph.D., a postdoctoral fellow at Fred Hutch Cancer Center, University of California, San Francisco and Parker Scholar at the Parker Institute for Cancer Immunotherapy. Dr. Lyu’s abstract, titled “Identification and therapeutic target of myeloid-mediated mechanisms of immunotherapy resistance in prostate cancer” was selected as a Top 100 abstract by 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,” 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.”
SITC Oral Presentation Overview and Key Data
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.
Dr. Fong is the scientific director of the Immunotherapy Integrated Research Center at Fred Hutch, where he is also a professor in the Translational Sciences and Therapeutics Division and a Bezos Family Distinguished Scholar in Immunotherapy.
The 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
- 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 clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com.
About Ciforadenant
Ciforadenant (CPI-444) is an investigational small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine to immune cells present in the tumor microenvironment. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2a receptor present on immune cells and block their activity. Ciforadenant has been shown to block the immunosuppressive effects of myeloid cells present in tumors and preclinical studies published in 2018 demonstrated synergy with combinations of anti PD1 and anti-CTLA4 antibodies.
Adenosine Gene Signature
The adenosine gene signature is a biomarker that reflects adenosine induced immunosuppression in the tumor. These genes express chemokines that recruit myeloid cells including immunosuppressive tumor associated myeloid cells, which are thought to mediate resistance to anti-PD-(L)1 treatment.
Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential efficacy of the Company’s product candidates including ciforadenant; the potential use of ciforadenant to treat metastatic renal cell cancer and mCRPC, including the potential to overcome resistance to immunotherapy; and the potential for the adenosine gene signature to select patients most likely to respond to treatment. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to risks detailed in the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2024, filed with the Securities and Exchange Commission on August 6, 2024, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of its product candidates; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company’s ability to enroll sufficient numbers of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
INVESTOR CONTACT:
Leiv Lea
Chief Financial Officer
Corvus Pharmaceuticals, Inc.
+1-650-900-4522
llea@corvuspharma.com
MEDIA CONTACT:
Sheryl Seapy
Real Chemistry
+1-949-903-4750
sseapy@realchemistry.com
FAQ
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