Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma

Phase 3

Not yet recruiting

• Conditions: Metastatic Clear Cell Renal Cell Carcinoma; Advanced Clear Cell Renal Cell Carcinoma
• Interventions: Drug: Casdatifan; Drug: Cabozantinib; Drug: Placebo

• Registration Number: NCT07011719
• Lead Sponsor: Arcus Biosciences, Inc.

Brief Summary

The purpose of the study is to evaluate the progression-free survival (PFS) of casdatifan versus placebo when each is given in combination with cabozantinib in adult patients with confirmed advanced or metastatic clear cell Renal Cell Carcinoma who have experienced progression on or after prior anti-PD-1 or anti-PD-L1 immunotherapy.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-02
• Study First Submitted QC: 2025-06-02
• Last Update Submitted: 2025-06-09
• Study First Posted: 2025-06-10
• Last Update Posted: 2025-06-12
• Study Start: 2025-07
• Primary Completion: 2028-04
• Study Completion: 2030-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 720

Inclusion Criteria

• Unresectable and measurable locally advanced or metastatic renal cell carcinoma with a primary clear cell component.
• A Karnofsky Performance Status (KPS) score ≥ 80%
• At least 1 target lesion measurable by computed tomography/magnetic resonance imaging per RECIST 1.1, not within a field of prior radiation therapy.
• Adequate organ and marrow function, ≤ 72 hours prior to randomization.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test.

Exclusion Criteria

• Received prior treatment with a HIF-2α inhibitor or cabozantinib.
• Other prior malignancy active within the previous year except for locally curable cancers that have been apparently cured.
• Clinically significant toxicities related to any prior anticancer treatment, or toxicities Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) regardless of relatedness to prior anticancer therapies.
• Uncontrolled or poorly controlled hypertension, as defined by a sustained blood pressure > 140/90 mm Hg on more than three antihypertensives
• History of leptomeningeal disease or spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (Experimental Arm)	Casdatifan	Casdatifan and cabozantinib taken orally
Arm A (Experimental Arm)	Cabozantinib	Casdatifan and cabozantinib taken orally
Arm B (Comparator Arm)	Cabozantinib	Placebo and cabozantinib taken orally
Arm B (Comparator Arm)	Placebo	Placebo and cabozantinib taken orally

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1	up to approximately 33 months

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1	up to approximately 33 months
Overall Survival (OS)	up to approximately 64 months
Duration of Response (DOR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1	up to approximately 33 months
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR)	up to approximately 33 months
The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)	up to approximately 33 months
Time to first symptom deterioration in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (NFKSI-DRS) Items 1-9 sub-scale score.	up to approximately 33 months