Randomized Phase 3 Trial of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arcus Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Jan 2026 → ongoing

Decision date (initial)

2025-11-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515023-11-00

ClinicalTrials.gov

NCT07011719

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare PFS of casdatifan + cabozantinib versus placebo + cabozantinib in all randomized patients.

Secondary objectives 4

1. To compare OS of casdatifan + cabozantinib versus placebo + cabozantinib in all randomized patients.
2. To assess additional measures of clinical activity in all randomized patients.
3. To assess the safety and tolerability of casdatifan or placebo in combination with cabozantinib in all patients treated.
4. To evaluate disease-related symptoms based on patient-reported outcomes using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index – 19 Item Version (NFKSI-19) of casdatifan + cabozantinib versus placebo + cabozantinib in all randomized patients.

Conditions and MedDRA coding

Advanced Clear Cell Renal Cell Carcinoma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 5

1. Received prior treatment with a HIF-2α inhibitor or cabozantinib.
2. Other prior malignancy active within the previous year except for locally curable cancers that have been apparently cured.
3. 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.
4. Uncontrolled or poorly controlled hypertension defined as a sustained blood pressure > 150 mmHg systolic or > 90 mmHg diastolic despite optimal antihypertensive treatment.
5. History of leptomeningeal disease or spinal cord compression.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as the time from date of randomization until progressive disease or death from any cause, whichever comes first, as assessed by BICR according to RECIST 1.1.

Secondary endpoints 6

1. OS is defined as the time from date of randomization until the date of death from any cause.
2. ORR is defined as the proportion of patients who have achieved confirmed complete response (CR) or confirmed partial response (PR) to study therapy, as assessed by BICR according to RECIST 1.1.
3. Duration of response is measured from the time of first response (CR or PR) until the date of first documented progressive disease or death, whichever comes first, as assessed by BICR according to RECIST 1.1.
4. Disease control rate (DCR) is defined as the proportion of patients who have achieved confirmed CR, confirmed PR, or stable disease for ≥ 16 weeks from date of randomization, as assessed by BICR according to RECIST 1.1.
5. The incidence and severity of treatment-emergent adverse events and treatment-emergent serious adverse events, and any clinically meaningful trends in safety parameters.
6. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arcus Biosciences Inc.

Sponsor organisation

Arcus Biosciences Inc.

Address

3928 Point Eden Way

City

Hayward

Postcode

94545-3719

Country

United States

Scientific contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Public contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Third parties 9

Locations

8 EU/EEA countries · 110 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications