Study of Zanzalintinib (XL092) + AB521 and Zanzalintinib + AB521 + Nivolumab in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Other Advanced Solid Tumors (STELLAR-009)

A Phase 1b/2 Dose-finding and Expansion Study Evaluating the Safety and Efficacy of Zanzalintinib (XL092) Combined With Either AB521 or AB521 Plus Nivolumab in Subjects With Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors.

The goal of this clinical trial is to learn about the safety and preliminary antitumor activity of zanzalintinib in combination with AB521 (doublet) and in combination with AB521 plus nivolumab (triplet) in participants with advanced ccRCC or other advanced solid tumors. The main questions it aims to answer are:

• The recommended doses (RDs)
• The safety and tolerability
• The PK and the preliminary efficacy

Study Overview

• Status: Recruiting
• Conditions: Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors
• Intervention / Treatment: Drug: zanzalintinib; Drug: AB521; Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Exelixis Clinical Trials; Phone Number: 1-888-EXELIXIS (888-393-5494); Email: druginfo@exelixis.com
• Study Contact Backup: Name: Backup or International; Phone Number: 650-837-7400

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Exelixis Clinical Site #1
  • New York
    • Port Jefferson Station, New York, United States, 11776
      • Recruiting
      • Exelixis Clinical Site #3
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Exelixis Clinical Site #2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants with unresectable advanced or metastatic disease or 1L or 2L+ clear cell Renal cell carcinoma.
2. Have not received HIF-2α targeted therapy previously.
3. Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al, 2009) as determined by the Investigator.
4. For all participants, archival tumor tissue material should be obtained; if archival tissue is not available or is older than 2 years, then a fresh biopsy should be obtained, if medically feasible. Specific requirements for tumor tissue samples will be described in the Laboratory Manual.
5. Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
6. Karnofsky Performance Status (KPS) ≥70%.
7. Screening ambulatory oxygen saturation (SpO2) ≥92%.
8. Screening left ventricular ejection fraction (LVEF) above the institutional lower limit of normal.

Key Exclusion Criteria:

1. Participants who have been previously treated with a HIF-2α targeted therapy and/or zanzalintinib.
2. Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Participants with clinically-relevant ongoing complications from prior radiation therapy are not eligible.
3. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
4. Concomitant anticoagulation with oral anticoagulants except for 1) prophylactic use of low-dose aspirin for cardioprotection or low dose low molecular weight heparins (LMWH) or 2) therapeutic doses of LMWH or specified direct factor Xa inhibitors.
5. Administration of a live, attenuated vaccine within 30 days prior to enrollment.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-finding Cohort A: Zanzalintinib + AB521; Participants with solid tumors will receive zanzalintinib + AB521	Drug: zanzalintinib; Specified doses on specified days; Other Names: XL092; Drug: AB521; Specified doses on specified days
Experimental: Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab; Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab	Drug: zanzalintinib; Specified doses on specified days; Other Names: XL092; Drug: AB521; Specified doses on specified days; Biological: Nivolumab; Specified doses on specified days; Other Names: OPDIVO®
Experimental: Expansion Cohort 1: Zanzalintinib + AB521; Participants with ccRCC will receive zanzalintinib + AB521	Drug: zanzalintinib; Specified doses on specified days; Other Names: XL092; Drug: AB521; Specified doses on specified days
Experimental: Expansion Cohort 2: zanzalintinib + AB521 + nivolumab; Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab	Drug: zanzalintinib; Specified doses on specified days; Other Names: XL092; Drug: AB521; Specified doses on specified days; Biological: Nivolumab; Specified doses on specified days; Other Names: OPDIVO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-finding Stage: Number of participants with dose-limiting toxicities (DLTs)	Up to 24 months
Expansion Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Dose-finding Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs) and immune-mediated adverse events (imAEs)	Up to 24 months
Dose-finding Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points	Up to 24 months
Dose-finding Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator	Up to 24 months
Expansion Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs), and immune-mediated adverse events (imAEs)	Up to 24 months
Expansion Stage: Duration of response (DOR) per RECIST 1.1 as assessed by the Investigator	Up to 24 months
Expansion Stage: Progression-free survival (PFS) per RECIST 1.1 as assessed by the Investigator	Up to 24 months
Expansion Stage: Overall survival (OS)	Up to 24 months
Expansion Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points	Up to 24 months

Collaborators and Investigators

• Sponsor: Exelixis
• Collaborators: Arcus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: XL092-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No