casdatifan (AB521) / Arcus Biosci - LARVOL DELTA

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

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 | "Clinical Trial Registration Number: NCT05536141 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

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

Arcus Biosciences to Present New Data from Casdatifan, a HIF-2a Inhibitor, in an Oral Presentation at the 2025 ASCO GU Symposium (Businesswire) - "Arcus Biosciences...announced that data from the ARC-20 study will be presented in a rapid oral session at the 2025...ASCO Genitourinary (GU) Cancers Symposium....The oral presentation will highlight safety and efficacy data from three cohorts of ARC-20, which evaluated casdatifan monotherapy in patients that had received both prior TKI and anti-PD-1 therapy. The presentation will include initial data for the 100mg QD tablet cohort...as well as updated data for the 50mg BID and 50mg QD expansion cohorts of ARC-20....'We are continuing to rapidly advance an extensive and robust development program for casdatifan, including the planned initiation of our first Phase 3 study (PEAK-1) in the first half of this year'....'We also look forward to presenting additional data from ARC-20 throughout the year'."

New P3 trial • P1 data • Clear Cell Renal Cell Carcinoma

Arcus To Report Updated ARC-20 Study Data On Casdatifan In Clear Cell Renal Cell Carcinoma In Q1 (RTTNews) - "The updated data, including median PFS, from the 100mg and 50mg expansion cohorts of the ARC-20 study, are expected to be presented in the first quarter of 2025....Multiple expansion cohorts are currently underway in the ARC-20 trial, including the 150mg and 100mg once-daily (QD) tablet cohorts of Casdatifan monotherapy, as well as the 100mg dose of Casdatifan in combination with Exelixis' approved drug Cabometyx ( Cabozantinib)."

P1 data • Trial status • Clear Cell Renal Cell Carcinoma

Stereodivergent Synthesis of the Vicinal Difluorinated Tetralin of Casdatifan Enabled by Ru-Catalyzed Transfer Hydrogenation. (PubMed, Org Lett) - "This process is easily scalable and amenable to highly functionalized substrates, as demonstrated here in the late-stage synthesis of casdatifan, a clinical-stage inhibitor of hypoxia-inducible factor-2α. Analysis of the physicochemical properties of casdatifan, which features a cis-vicinal difluoride, revealed a higher level of facial polarization compared to its trans-vicinal difluoride isomers."

Journal

Arcus Biosciences Reports Third-Quarter 2024 Financial Results and Provides a Pipeline Update (Businesswire) - "Upcoming Casdatifan Milestones: Multiple expansion cohorts of ARC-20 evaluating casdatifan in ccRCC as a monotherapy and in combination with cabozantinib in ccRCC are underway with additional data presentations expected in the next 12 months. (i) 100mg (50mg twice daily (BID), capsules) and 50mg expansion cohorts: Updated data, including median PFS, are expected to be presented in the first quarter of 2025; (ii) 150mg and 100mg (once daily (QD), tablets) expansion cohorts: Initial data are expected to be presented in 2025; (iii) 100mg of casdatifan plus cabozantinib: Safety data are expected to be presented in 2025."

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

Casdatifan Demonstrates Durable Activity in Metastatic Clear Cell Renal Cell Carcinoma (OncLive) - "'Based on our experience in the ARC-20 study, we have seen casdatifan’s ability to quickly bring tumor growth under control and its high response and disease control rates,' Toni K. Choueiri, MD..."

Media quote • Renal Cell Carcinoma

Toni Choueiri on casdatifan in kidney cancer: ENA24 | Dana-Farber Cancer Institute (YouTube) - "Kidney cancer research: HIF-2a inhibitor, casdatifan, shrunk tumors and shows promising clinical activity in patients with advanced kidney cancer, according to research presented by Toni Choueiri, MD..."

Video • Renal Cell Carcinoma

First Clinical Data for Arcus Biosciences’ HIF-2a Inhibitor, Casdatifan, Showed Promising Clinical Activity and Tumor Shrinkage in Patients with Metastatic Kidney Cancer (Businesswire) - P1 | N=302 | ARC-20 (NCT05536141) | Sponsor: Arcus Biosciences, Inc. | "In the dose escalation (20mg to 200mg) portion of the study, the safety profile was comparable across the doses; there were no dose-limiting toxicities, and the maximum tolerated dose was not reached at daily doses of up to 150 mg (200 mg portion of the study is currently ongoing)...Casdatifan showed a rapid time to response, and only 19% of patients had primary progressive disease (progressed at or before their first disease assessment). The majority of patients (81%) experienced disease control with either a partial response or stable disease. At the time of the DCO, the median progression-free survival had not been reached. 34% of patients experienced an objective response, meaning their tumor shrank by at least 30%."

P1 data • Oncology • Renal Cell Carcinoma • Solid Tumor