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

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 720 participants

Study Arms

• Arm A (Experimental Arm) (EXPERIMENTAL)
  Casdatifan and cabozantinib taken orally
• Arm B (Comparator Arm) (PLACEBO_COMPARATOR)
  Placebo and cabozantinib taken orally

Interventions

• DRUG: Casdatifan — Administered as specified in the treatment arm
• DRUG: Cabozantinib — Administered as specified in the treatment arm
• DRUG: Placebo — Administered as specified in the treatment arm

Primary Outcomes

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

Secondary Outcomes

• Overall Survival (OS) (up to approximately 64 months)
• Objective Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 (up to approximately 33 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)

Eligibility Criteria

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, ≤ 1 week 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.
* Ongoing 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, defined as a sustained blood pressure \> 150 mmHg systolic or \> 90 mmHg diastolic despite optimal antihypertensive treatment.
* History of leptomeningeal disease or spinal cord compression.

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

Trial Locations

• Research Site, Gilbert, Arizona, United States
• Research Site, Goodyear, Arizona, United States
• Research Site, Phoenix, Arizona, United States
• Research Site, Duarte, California, United States
• Research Site, La Jolla, California, United States
• Research Site, Los Angeles, California, United States
• Research Site, Sacramento, California, United States
• Research Site, San Diego, California, United States
• Research Site, New Haven, Connecticut, United States
• Research Site, Jacksonville, Florida, United States
• ...and 10 more locations

Contact Information

• Medical Director — CONTACT
  Phone: +1-510-462-3330
  Email: clinicaltrials@arcusbio.com

Study Officials

• Medical Director — STUDY_DIRECTOR
  Arcus Biosciences

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