casdatifan (AB521) / Arcus Biosciences, Otsuka, Taiho - LARVOL DELTA

Evaluation of peripheral biomarkers in ccRCC patients treated with the HIF-2α inhibitor casdatifan (ESMO 2026) - No abstract available

Biomarker • Clinical • Clear Cell Renal Cell Carcinoma • Oncology • EPAS1

Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Vanderbilt-Ingram Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2029 ➔ Sep 2026

Enrollment open • Trial initiation date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC-20: A phase 1, open-label dose-escalation and expansion study (EORTC-NCI-AACR 2024) - P1 | "These preliminary findings indicate that cas was well tolerated with no DLTs observed, and the MTD was not reached. Cas demonstrated promising durable clinical activity, ORR and DCR in heavily pre-treated ccRCC pts and warrants further investigation."

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

Episode 517: Casdatifan Clinical Data in RCC and Translational Correlates (GU Oncology Now) - "Toni Choueiri joins Brian and Tom to discuss a recent Nature paper regarding the novel HIF inhibitor, casdatifan, and biomarkers of response."

Audio • Biomarker • Renal Cell Carcinoma

Arcus Biosciences to Host Investor Event Featuring New Data for Casdatifan as a Treatment for Kidney Cancer Across Multiple Lines of Therapy (Businesswire) - "The event will highlight new data from the ARC-20 platform study, which is evaluating casdatifan...for clear cell renal cell carcinoma (ccRCC)...New data to be presented will include: First-line TKI-free combinations: Casdatifan plus zimberelimab...Casdatifan plus ipilimumab plus zimberelimab...Safety data from this cohort will support initiation of the first-line registrational trial PEAK-20, evaluating casdatifan plus ipilimumab plus nivolumab, expected to occur in the fourth quarter of 2026...Second-line TKI-containing combination: Casdatifan plus cabozantinib....Casdatifan monotherapy....Arcus will also be highlighting new subgroup analyses, including evaluation of casdatifan monotherapy efficacy for both PFS and OS by prior therapy. In addition, Arcus will share the first translational data correlating pharmacodynamic markers of HIF-2α inhibition with overall survival....to initiate the Phase 3 PEAK-20 study in first-line metastatic ccRCC by year-end 2026."

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

Activity and biomarker analyses with casdatifan (cas), a next-generation HIF-2α inhibitor, in refractory clear cell renal cell carcinoma (ccRCC): Results from ARC-20. (ASCO-GU 2026) - P1 | "In heavily treated metastatic ccRCC, Cas monotherapy showed encouraging clinical activity and durable responses across cohorts. The extent of sEPO reduction correlated with clinical benefit, providing important linkage between tumor HIF-2α biology and clinical outcomes. The safety profile of Cas monotherapy remains manageable, supporting evaluation of the 100 mg QD dose now in phase 3 development."

Biomarker • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1

Comparative PK Assessment Study of Casdatifan in Moderate Hepatically Impaired Participants Versus Matched Participants With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

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

PEAK-1: A randomized, double-blind, active-control, multicenter phase 3 trial of casdatifan and cabozantinib versus placebo and cabozantinib in patients with advanced clear cell renal cell carcinoma. (ASCO 2026) - P3 | "Pt reported outcomes using NFKSI-DRS will also be assessed. Enrolment is ongoing as of 1 Oct 2025."

Clinical • Metastases • P3 data • Cardiovascular • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hypertension • Oncology • Solid Tumor • AXL • CYP3A4 • EPAS1

A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Other Agents in Participants With Advanced Renal Cell Carcinoma (RCC) (ROSETTA RCC-208) (clinicaltrials.gov) - P1/2 | N=474 | Recruiting | Sponsor: Bristol-Myers Squibb | N=254 ➔ 474

Enrollment change • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Casdatifan shows durable response linked to HIF-2α biology in kidney cancer. (PubMed, Nature) - P1 | "Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2α pathway modulation, tumour biology and clinical efficacy."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hematological Disorders • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EPAS1 • EPO

Safety Profile of Casdatifan Monotherapy in Patients with Clear Cell Renal Cell Carcinoma: Pooled Analysis of the ARC-20 Study (NCT05536141) (KCRS 2026) - P1, P3 | "Among patients with anemia, those treated with ESAs had a longer mPFS than those treated with transfusions, regardless of ESA use, suggesting that ESA use did not negatively affect mPFS. Keywords Casdatifan, Hypoxia-inducible factor 2-a, Safety profile, Clear cell renal cell carcinoma"

Monotherapy • Retrospective data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hematological Disorders • Oncology • Solid Tumor • EPAS1

A HIF-2α activity signature highlights the therapeutic potential of casdatifan as an HCC treatment (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Hepatocellular Cancer • Oncology • EPAS1

Hypoxia-inducible factor-2α inhibition with casdatifan combines with checkpoint receptor modulation to enhance tumor control (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Oncology

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

PEAK-1 (NCT07011719): A Randomized, Double-Blind, Active-Control Phase 3 Trial of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients with Advanced Clear Cell Renal Cell Carcinoma (KCRS 2026) - P3 | "The casdatifan plus cabozantinib combination is a novel treatment approach for patients with ccRCC in the post–first-line setting. Conclusions N/A Keywords Clear cell renal cell carcinoma, HIF-2α inhibitor, Casdatifan, Cabozantinib"

Clinical • Metastases • P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hypertension • Oncology • Renal Cell Carcinoma • Solid Tumor • AXL • CYP3A4 • EPAS1

A Bioequivalence Study Between Two Casdatifan Tablet Strengths and Food Effect Study of Casdatifan in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Completed

Trial completion

Arcus expects multiple data readouts for casdatifan in 2026 (Businesswire) - "In first-line ccRCC, initial data from the ARC-20 cohorts evaluating casdatifan in early-line settings, including early efficacy data for the cohort evaluating casdatifan plus zimberelimab and early safety data for the cohort evaluating casdatifan plus zimberelimab plus ipilimumab in first-line ccRCC. In second-line IO-experienced ccRCC, more mature overall response rate data and initial PFS data, including Kaplan-Meier curve(s), for approximately 45 patients treated in the ARC-20 cohort evaluating casdatifan plus cabozantinib. All patients will have had at least 18 months of follow-up. In late-line ccRCC, updated data from the ARC-20 monotherapy cohorts, including overall survival data."

P1 data • Clear Cell Renal Cell Carcinoma

New Clinical Collaborations: (Businesswire) - "Bristol Myers Squibb (BMS): Casdatifan combinations will be added as two new arms of the BMS-sponsored Phase 1/2 ROSETTA RCC-208 study in advanced RCC, evaluating casdatifan in combination with the anti-PD-L1/VEGF-A bispecific antibody pumitamig, which is being jointly developed by BioNTech and BMS....Arcus has also executed one additional clinical collaboration agreement to evaluate a casdatifan combination with another anti-PD-x/VEGF bispecific antibody in first-line ccRCC, which is expected to initiate in the fourth quarter of 2026."

Licensing / partnership • Renal Cell Carcinoma

Enrollment in PEAK-1, the global Phase 3 study evaluating casdatifan plus cabozantinib versus cabozantinib alone in IO-experienced metastatic ccRCC, is accelerating, and Arcus remains on track to complete enrollment by year-end 2026 (Businesswire)

Enrollment status • Clear Cell Renal Cell Carcinoma

Development Program: Late-Line ccRCC (Businesswire) - "A new randomized ARC-20 cohort will evaluate casdatifan plus tivozanib versus tivozanib alone in patients who received two or more lines of prior therapy, including a belzutifan-containing regimen, which will elucidate the impact of prior HIF-2α inhibitor treatment on casdatifan’s activity. Enrollment in this new ARC-20 cohort is expected to begin in the fourth quarter of 2026."

Trial status • Clear Cell Renal Cell Carcinoma

Development Program: First-Line ccRCC (Businesswire) - "...PEAK-20, evaluating casdatifan plus nivolumab plus ipilimumab in the first-line setting, which is expected to initiate by year-end 2026. TKI-containing (casdatifan plus IO/TKI): A casdatifan-based regimen inclusive of the well-established TKI axitinib, for those circumstances where physicians prefer to have a TKI-inclusive therapy, with an ARC-20 cohort expected to begin in the fourth quarter of 2026. Novel TKI-free bispecific combinations (see New Clinical Collaborations above): Casdatifan in combination with anti-PD-x/VEGF bispecifics pumitamig, ivonescimab and one additional antibody with study initiations expected prior to the end of the year."

New P3 trial • New trial • Trial status • Clear Cell Renal Cell Carcinoma

Casdatifan Partnership Updates (Businesswire) - "Arcus will receive a $15 million milestone payment from Taiho Pharmaceutical in the third quarter, triggered by PEAK-1 enrollment in Japan, under the parties’ option and license agreement. Taiho holds rights to casdatifan in Japan and certain territories in Asia."

Financing • Clear Cell Renal Cell Carcinoma

Comparative PK Assessment Study of Casdatifan in Moderate Hepatically Impaired Participants Versus Matched Participants With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Arcus Biosciences, Inc.

New P1 trial • Hepatology

Pilot Study of Casdatifan-Treated Refractory Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Vanderbilt-Ingram Cancer Center

New P1 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor