- Treatment with casdatifan, a HIF-2a inhibitor, plus cabozantinib, a tyrosine kinase inhibitor, showed a confirmed overall response rate (ORR) of 46% in patients who reached a minimum of 12 weeks (two scans) of follow-up
- The combination had a manageable safety profile, and there was no meaningful overlapping toxicity for the two drugs
- These data support the initiation of PEAK-1, a Phase 3 study that will evaluate casdatifan plus cabozantinib in immunotherapy-experienced clear cell renal cell carcinoma (ccRCC) patients, and eVOLVE-RCC02, a Phase 1b/3 study in first-line ccRCC patients, both of which will begin shortly
- Arcus will host a conference call to discuss these data at 5:00 AM PT / 7:00 AM CT on Monday, June 2, 2025
HAYWARD, Calif.–(BUSINESS WIRE)–Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, today presented the first data for casdatifan plus cabozantinib in an oral presentation by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
“I was very encouraged to see that nearly half of patients had a confirmed response to the casdatifan plus cabozantinib combination despite short follow-up,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School, and lead investigator of ARC-20. “Casdatifan plus cabozantinib was well tolerated, and the safety profile was consistent with that of either agent alone, supporting their potential as a combination therapy. I look forward to enrolling patients into the PEAK-1 trial as soon as it is open.”
“The initial data for casdatifan plus cabozantinib in the ARC-20 study have already exceeded the historic benchmarks for either agent alone, as well as that of another HIF-2a inhibitor plus cabozantinib in the same second-line setting,” said Terry Rosen, Ph.D., chief executive officer of Arcus. “These data serve as the proof of concept for PEAK-1, which will be initiated in the coming weeks and is designed to generate evidence to change the standard of care for people who have progressed on prior immunotherapy treatment.”
ARC-20 is a Phase 1/1b dose-escalation and expansion study that includes a cohort evaluating once-daily 100mg of casdatifan plus 60mg of cabozantinib in patients with ccRCC who had progressed on prior immunotherapy. At the time of the data cutoff (DCO, March 14, 2025), 42 participants were evaluable for safety, and 24 reached at least 12 weeks of follow-up and were evaluable for efficacy. Among the safety-evaluable population (N=42), most participants (79%) had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate or poor. Nearly half (46%) of the efficacy-evaluable population (N=24) achieved a confirmed response per RECIST 1.1, and only one patient had primary progressive disease. The vast majority of the efficacy-evaluable population remains on treatment.
In the safety-evaluable population, no unexpected safety risks were identified at the time of DCO, and casdatifan plus cabozantinib had an acceptable safety profile with no meaningful overlapping toxicity for the two drugs. Only two patients discontinued any drug, and no patients discontinued treatment with both drugs. The incidence of treatment-emergent adverse events (TEAEs) with casdatifan, particularly anemia and hypoxia, was similar to TEAEs observed with casdatifan monotherapy, and there were no casdatifan-related Grade 4 or 5 adverse events. The incidence of TEAEs associated with each drug was consistent with what is expected for each drug alone.
A summary of the efficacy and safety results is below.
| Efficacy-Evaluablea | casdatifan 100mg QD + cabozantinib 60mg QD (n=24) |
| Median Follow-Up | 5.3 months |
| Confirmed ORR (cORR) per RECIST v1.1 [95% CI] | 46% (11)b |
| [26,67] | |
| Best Overall Response: |
|
| Complete Response | 4% (1) |
| Partial Response | 42% (10)b |
| Stable Disease | 50% (12) |
| Progressive Disease | 4% (1) |
| CI: confidence interval; QD: daily | |
| a All eligible patients who received any study treatment and reached a minimum of 12 weeks follow-up or discontinued due to progression or death. | |
| b Inclusive of one patient who had partial response confirmation after March 14, 2025. | |
| Safetya | casdatifan 100mg QD + cabozantinib 60mg QD (n=42) | |
|
| casdatifan | cabozantinib |
| Patients with any Treatment-Related Grade ≥3 AEb |
|
|
| Anemia | 24% (10) | 14% (6) |
| Hyponatremia | 0 | 7% (3) |
| Hypoxia | 7% (3) | 0 |
| Hypertension | 0 | 5% (2) |
| Neutrophil count decrease | 2% (1) | 5% (2) |
| Patients with any AE leading to dose reductionb |
|
|
| Fatigue | 2% (1) | 12% (5) |
| Anemia | 10% (4) | 2% (1) |
| Hypoxia | 10% (4) | 0 |
| Palmar-plantar erythrodysesthesia | 0 | 5% (2) |
| Stomatitis | 0 | 5% (2) |
| AE: adverse event | ||
| a Safety population included patients who received any amount of study drug and had at least one month of safety follow-up at the data cutoff date. | ||
| b Treatment-emergent adverse events (grade 3 or higher) related to casdatifan, cabozantinib, or any study drug reported in ≥3% of patients in any treatment arm. | ||
Arcus is pursuing a broad development program in both the immuno-oncology (IO)-naive and post-IO settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. These studies include:
- Arcus’s planned Phase 3 study, PEAK-1, which will evaluate casdatifan plus cabozantinib versus cabozantinib monotherapy as a first- or second-line treatment in patients with metastatic ccRCC who have previously received anti-PD-1/PD-L1 therapy. The primary endpoint will be PFS with a key secondary endpoint of overall survival.
- eVOLVE-RCC02, a Phase 1b/3 study sponsored by AstraZeneca, which will evaluate casdatifan plus volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody, as first-line treatment for participants with ccRCC.
- ARC-20, which includes three cohorts evaluating casdatifan in earlier-line settings, including casdatifan plus zimberelimab in first-line ccRCC, casdatifan monotherapy in favorable risk ccRCC, and casdatifan monotherapy in immunotherapy-experienced, TKI-naive settings.
Investors may dial in to the conference call at +1 404 975 4839 (local) or +1 833 470 1428 (toll-free) using Conference ID: 446724 on Monday, June 2, 2025, at 5:00 AM PT / 7:00 AM CT. Participants may also register for the call online using the following link: https://events.q4inc.com/attendee/154065244. To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.
About Casdatifan (AB521)
Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor responsible for activating multiple tumor growth pathways in hypoxic and pseudo-hypoxic tumor environments. By selectively binding HIF-2a, casdatifan is designed to shut down hypoxic oncogenesis and key oncogenic pathways, which leads to cancer cell death. Clear cell renal cell carcinoma is almost universally associated with HIF-2a dysregulation. Casdatifan is currently being evaluated in ARC-20, a Phase 1/1b study in renal cell carcinoma.
Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established.
About RCC
According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 80,980 Americans will be diagnosed with kidney cancer in 2025. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination therapies for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including domvanalimab, an Fc-silent anti-TIGIT antibody being studied in combination with zimberelimab, an anti-PD-1 antibody, for upper gastrointestinal and non-small cell lung cancer, casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.
Forward Looking Statements
This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the statements in Dr. Choueiri’s and Dr. Rosen’s quotes and statements regarding: the potency, efficacy or safety of casdatifan, including its potential for a best-in-class profile and potential as a combination therapy; and Arcus’s development plans for the casdatifan program, including expected timing and design for new studies and cohorts and plans for generating data to support initiation of future studies. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to risks associated with: interim data not being replicated in future studies evaluating the same investigational molecules or regimen; the unexpected emergence of adverse events or other undesirable side effects with casdatifan; risks associated with manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; difficulties associated with the management of the collaboration activities with our strategic partners or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release except to the extent required by law.
The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.
Contacts
Investor Inquiries:
Pia Eaves
VP of Investor Relations & Strategy
(617) 459-2006
peaves@arcusbio.com
Media Inquiries:
Holli Kolkey
VP of Corporate Affairs
(650) 922-1269
hkolkey@arcusbio.com
Maryam Bassiri
AD, Corporate Communications
(510) 406-8520
mbassiri@arcusbio.com
