casdatifan (AB521) / Arcus Biosci - LARVOL DELTA

Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P3 | N=720 | Not yet recruiting | Sponsor: Arcus Biosciences, Inc.

New P3 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study of Zanzalintinib (XL092) + AB521 and Zanzalintinib + AB521 + Nivolumab in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Other Advanced Solid Tumors (STELLAR-009) (clinicaltrials.gov) - P1 | N=25 | Terminated | Sponsor: Exelixis | Phase classification: P1/2 ➔ P1 | Trial completion date: Jan 2027 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ May 2025; The study was terminated prior to starting the Phase 2 portion due to a business decision.

Phase classification • Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

ARC-20: Casdatifan Plus Cabozantinib Expansion Cohort (YouTube) - "Brad McGregor, MD...opens up about the expansion cohort of the phase 1 ARC-20 study, which looked at combination casdatifan plus cabozantinib in previously treated patients with clear cell renal cell carcinoma."

Video

eVOLVE-RCC02: A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC (clinicaltrials.gov) - P3 | N=1116 | Not yet recruiting | Sponsor: AstraZeneca

Monotherapy • New P3 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Combination casdatifan plus cabozantinib expansion cohort of phase 1 ARC-20 study in previously treated patients with clear cell renal cell carcinoma. (ASCO 2025) - P1 | "In previously treated patients with ccRCC, casdatifan 100 mg in combination with cabozantinib 60 mg had a manageable AE profile with promising clinical activity. These data support continued evaluation of this combination in the phase 3 PEAK-1 clinical trial."

Clinical • IO biomarker • P1 data • Anemia • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1

Initial Data from the ARC-20 Study of Casdatifan Plus Cabozantinib Showed Nearly Half of Patients with Metastatic Kidney Cancer Had a Confirmed Response (BioSpace) - "'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."

Media quote

Initial Data from the ARC-20 Study of Casdatifan Plus Cabozantinib Showed Nearly Half of Patients with Metastatic Kidney Cancer Had a Confirmed Response (Arcus Biosciences Press Release) - P1/1b | N=302 | ARC-20 (NCT05536141) | Sponsor: Arcus Biosciences, Inc. | "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."

P1 data • Clear Cell Renal Cell Carcinoma

Casdatifan (AB521) is a novel and potent allosteric small molecule inhibitor of protumourigenic HIF-2α dependent transcription. (PubMed, Br J Pharmacol) - "AB521 is a potent, selective and orally bioavailable HIF-2α inhibitor, with favourable pharmacological properties, that is being explored clinically for the treatment of ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • EPAS1 • HIF1A • VHL

Arcus Biosciences Reports First-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights: Casdatifan (HIF-2a inhibitor):...Upcoming Study and Cohort Initiations: (i) The PEAK-1 Phase 3 study evaluating casdatifan plus cabozantinib versus cabozantinib in IO-experienced ccRCC is expected to initiate in the second quarter of 2025; (ii) Shortly thereafter, Arcus and AstraZeneca expect to initiate a clinical study, part of AstraZeneca’s eVOLVE portfolio, evaluating casdatifan plus volrustomig, AstraZeneca’s investigational anti-PD-1/CTLA-4 bispecific antibody, in IO-naive ccRCC. This study will be operationalized by AstraZeneca."

New trial • Clear Cell Renal Cell Carcinoma

Arcus Biosciences Reports First-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights: Casdatifan (HIF-2a inhibitor):...Planned Data Readouts: (i) June 2025: Safety and initial efficacy data for the ARC-20 cohort evaluating casdatifan plus cabozantinib in IO-experienced patients will be presented in an oral session at the ASCO Annual Meeting; (ii) Fall 2025: More mature data from the cohorts evaluating casdatifan monotherapy in patients who had progressed on both an anti-PD-1 and a TKI therapy; (iii) 2026: More mature data from the casdatifan plus cabozantinib cohort and initial data from the new ARC-20 cohorts evaluating casdatifan in the first-line (1L) and IO-experienced settings."

P1 data • Clear Cell Renal Cell Carcinoma

Arcus Biosciences to Present First Combination Data for HIF-2a Inhibitor Casdatifan Plus Cabozantinib in an Oral Presentation at the 2025 ASCO Annual Meeting (Businesswire) - "The oral presentation will highlight the first safety and efficacy data for the ARC-20 expansion cohort evaluating the HIF-2a inhibitor casdatifan plus cabozantinib, an anti-vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor (VEGFR2-TKI), in patients with ccRCC that had previously been treated with immunotherapy alone or in combination with anti-VEGFR2-TKI therapies....The ASCO presentation will include a more mature data cut than that described in the abstract and will include safety and initial efficacy data for the 100mg casdatifan once-daily (QD) plus 60mg cabozantinib QD cohort."

P1 data • Clear Cell Renal Cell Carcinoma

Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas. (PubMed, Am Soc Clin Oncol Educ Book) - "HIF-2α inhibition represents a breakthrough in targeting the fundamental pathobiology of clear cell RCC, with belzutifan demonstrating significant clinical benefit in both von Hippel-Lindau disease and sporadic RCC...ADCs have become a cornerstone of UC treatment, with enfortumab vedotin plus pembrolizumab now approved as first-line therapy. Multiple human epidermal growth factor receptor 2 (HER2)-directed ADCs have shown efficacy in HER2-expressing UC, including trastuzumab deruxtecan, which recently received tumor-agnostic approval. While ADC development in RCC faces unique challenges, novel approaches including immunostimulatory payloads and bispecific antibodies are being explored. The integration of these advances in molecular imaging and therapeutics offers opportunities for more personalized treatment approaches in RCC and UC."

Journal • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • Von Hippel-Lindau Syndrome • CA9 • EPAS1 • HER-2 • NECTIN4

Arcus's first Class 1 new drug was submitted for clinical trial in China [Google translation] (Sina Corp) - "On April 9, the CDE announced that the clinical trial application for casdatifan tablets, a Class 1 new drug submitted by Arcus Biosciences, was accepted. This is the first time that the drug has applied for IND in China. Casdatifan is a HIF-2α inhibitor that can block the transcription of HIF-2α-dependent genes."

New trial • Solid Tumor

Drug-Drug Interaction Study of Casdatifan in Healthy Adult Participants (ARC-29) (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Arcus Biosciences, Inc.

New P1 trial

OmniAb Reports Fourth Quarter and Full Year 2024 Financial Results and Business Highlights (Businesswire) - "Zimberelimab:..Arcus Biosciences...expects to initiate three new expansion cohorts within the Phase 1/1b ARC-20 study in the first quarter of 2025, including one cohort for casdatifan plus zimberelimab in all-comer first-line clear cell renal cell carcinoma."

Trial status • Clear Cell Renal Cell Carcinoma

Casdatifan Monotherapy Shows Early Efficacy Signals and Tolerable Safety Profile in Pretreated ccRCC (OncLive) - P1/1b | N=302 | ARC-20 (NCT05536141) | Sponsor: Arcus Biosciences, Inc. | "Data from the dose-escalation and -expansion portions of the study were presented by Toni K. Choueiri, MD, FASCO, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts. The median follow-up was 15 months (range, 7 to 19+ months), 12 months (range, 9 to 14+ months), and 5 months (range, 2 to 6+ months) in the 50 mg twice daily (n = 33), 50 mg per day (n = 31), and 100 mg per day (n = 29) casdatifan cohorts, respectively. The confirmed overall response rates (ORRs) were 25% (95% CI, 11.5%-43.4%), 29% (95% CI, 13.2%-48.7%), and 33% (95% CI, 16.5%-54.0%) in the 50 mg twice daily, 50 mg per day, and 100 mg per day cohorts, respectively. Best overall response was observed in 10 (31%), 9 (32%), and 9 (33%) patients, respectively."

P1 data • Clear Cell Renal Cell Carcinoma • Von Hippel-Lindau Syndrome

Arcus Biosciences Reports Fourth-Quarter and Full-Year 2024 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights: Casdatifan (HIF-2a inhibitor):...Upcoming Study and Cohort Initiations: Three new expansion cohorts within ARC-20 will be initiated in the first quarter of 2025: (i) Casdatifan plus zimberelimab in all-comer 1L ccRCC; (ii) Casdatifan monotherapy in favorable-risk 1L ccRCC; (iii) Casdatifan monotherapy in the IO-experienced setting for patients with ccRCC who have not received a VEGFR-TKI therapy."

Trial status • Clear Cell Renal Cell Carcinoma

Casdatifan is linked with promising safety, efficacy in clear cell RCC (Urology Times) - "In terms of AEs, Choueiri reported that casdatifan appeared to be well tolerated, with a comparable safety profile for the 3 dosage regimens. Any treatment-emergent AEs (TEAEs) were observed in 32 (97%) patients, 30 (90%) patients, and 28 (97%) patients in the 50 mg twice daily, 50 mg/day, and 100 mg/day regimens, respectively. TEAEs related to casdatifan were observed in 31 (94%) patients, 28 (90%) patients, and 27 (93%) patients in the 50 mg twice daily, 50 mg/day, and 100 mg/day regimens, respectively."

Media quote • Renal Cell Carcinoma

ARC-20: Casdatifan for Patients With Previously Treated ccRCC (YouTube) - "Brad McGregor, MD...explains the safety, efficacy, and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study of casdatifan monotherapy in patients with previously treated clear cell renal cell carcinoma."

Video

ARC-20: casdatifan monotherapy in pre-treated clear cell renal cell carcinoma (YouTube) - "Bradley McGregor, MD...discusses results from the Phase I ARC-20 trial (NCT05536141) of casdatifan monotherapy in patients with clear cell renal cell carcinoma (ccRCC) previously treated with PD-(L)1 and VEGFR-TKI therapies. Casdatifan showed promising activity across all risk groups, with manageable safety signals, including anemia and hypoxia. Based on these findings, casdatifan will be investigated in combination with cabozantinib in the Phase III PEAK-1 trial."

Interview • Video

ARC-20: A Phase 1 Study of AB521 Monotherapy and Combination Therapies in Renal Cell Carcinoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=302 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jan 2026 ➔ Jul 2027 | Trial primary completion date: Jan 2026 ➔ Jul 2027

Monotherapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Expected milestones for casdatifan in 2025 and 2026 are: (Businesswire) - "(i) Q2 2025: To initiate PEAK-1, which will evaluate casdatifan plus cabozantinib versus cabozantinib in the IO-experienced metastatic ccRCC setting. The primary endpoint will be PFS; (ii) Mid-2025: To present initial safety and efficacy data from the casdatifan plus cabozantinib cohort of ARC-20; (iii) Fall 2025: To share more mature results for the casdatifan monotherapy cohorts of ARC-20; (iv) 2025: To initiate a Phase 1b study, part of the eVOLVE portfolio, which AstraZeneca will operationalize, to evaluate casdatifan plus volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody, in ccRCC patients who are IO-naive...; (v) 2026: To share initial data from newly added cohorts of ARC-20 evaluating casdatifan monotherapy in favorable risk first-line (1L) ccRCC, casdatifan plus zimberelimab in 1L ccRCC and casdatifan monotherapy in IO-experienced/TKI-naive ccRCC."

New trial • P1 data • Clear Cell Renal Cell Carcinoma

Arcus Biosciences Retains Rights to Casdatifan, a Potential Best-in-Class HIF-2a Inhibitor, and Announces Pricing of $150 Million Common Stock Offering (Businesswire) - "Arcus Biosciences...announced that Gilead’s time-limited exclusive option rights to casdatifan have expired. In addition, Arcus has announced the pricing of a $150 million common stock offering, which is subject to customary closing conditions and includes participation from new and existing institutional healthcare investors and Gilead. Today’s financing is expected to fund Arcus through the anticipated data readout for PEAK-1, the Phase 3 trial for casdatifan in the immuno-oncology (IO)-experienced ccRCC setting. This financing, combined with the world class development and regulatory expertise that Arcus has already established, will enable Arcus to rapidly advance casdatifan and maintain the momentum for this program that Arcus has independently built to date."

Commercial • Clear Cell Renal Cell Carcinoma

Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. (ASCO-GU 2025) - P1 | "In heavily pretreated pts with ccRCC, Cas monotherapy was well tolerated with promising early clinical activity across IMDC risk groups. Cas 100 mg QD will be combined with VEGFR-TKI (cabozantinib) in the phase 3 PEAK-1 trial and immunotherapy (volrustomig) in a separate upcoming first-line trial. aEfficacy-evaluable pts: all pts who had measurable disease at BL, received ≥1 dose and had ≥1 post-BL efficacy assessment, or who discontinued study treatment due to progression or death."

Clinical • IO biomarker • Monotherapy • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1 • HIF1A

New Data Demonstrated Best-in-Class Potential for Casdatifan, a HIF-2a Inhibitor, in Patients with Metastatic Kidney Cancer (Businesswire) - P1/1b | N=302 | ARC-20 (NCT05536141) | Sponsor: Arcus Biosciences, Inc. | "Arcus Biosciences...presented new data for casdatifan...in an oral plenary session...at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium....A 9.7-month median progression-free survival (mPFS) was reached for the 50mg twice-daily (BID) casdatifan monotherapy cohort of the Phase 1/1b ARC-20 study; mPFS was not yet reached for other cohorts. Across all three monotherapy cohorts presented, casdatifan demonstrated improvements in the rate of primary progression, overall response rate (ORR) and progression-free survival (PFS) relative to published data from studies with HIF-2a inhibitors to date....No unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile across all doses....'We look forward to sharing initial results for the casdatifan plus cabozantinib cohort later this year'."

P1 data • Renal Cell Carcinoma