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)

NCT06191796 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: XL092-009
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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

Study Arms (4)

Dose-finding Cohort A: Zanzalintinib + AB521

EXPERIMENTAL

Participants with solid tumors will receive zanzalintinib + AB521

Drug: zanzalintinib; Drug: AB521

Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab

EXPERIMENTAL

Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab

Drug: zanzalintinib; Drug: AB521; Biological: Nivolumab

Expansion Cohort 1: Zanzalintinib + AB521

EXPERIMENTAL

Participants with ccRCC will receive zanzalintinib + AB521

Drug: zanzalintinib; Drug: AB521

Expansion Cohort 2: zanzalintinib + AB521 + nivolumab

EXPERIMENTAL

Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab

Drug: zanzalintinib; Drug: AB521; Biological: Nivolumab

Interventions

zanzalintinib DRUG

Specified doses on specified days

Also known as: XL092

Dose-finding Cohort A: Zanzalintinib + AB521; Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab; Expansion Cohort 1: Zanzalintinib + AB521; Expansion Cohort 2: zanzalintinib + AB521 + nivolumab

AB521 DRUG

Specified doses on specified days

Dose-finding Cohort A: Zanzalintinib + AB521; Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab; Expansion Cohort 1: Zanzalintinib + AB521; Expansion Cohort 2: zanzalintinib + AB521 + nivolumab

Nivolumab BIOLOGICAL

Specified doses on specified days

Also known as: OPDIVO®

Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab; Expansion Cohort 2: zanzalintinib + AB521 + nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a).unresectable advanced or metastatic solid tumor; b). unresectable advanced or metastatic clear cell renal cell carcinoma and no prior anticancer therapy; or c). unresectable advanced or metastatic clear cell renal cell carcinoma and has received at least one prior anticancer therapy.
• 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.
• 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.
• 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.
• Karnofsky Performance Status (KPS) ≥70%.
• Screening ambulatory oxygen saturation (SpO2) ≥92%.
• Screening left ventricular ejection fraction (LVEF) above the institutional lower limit of normal.

You may not qualify if:

• Participants who have been previously treated with a HIF-2α targeted therapy and/or zanzalintinib.
• 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.
• 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.
• Concomitant anticoagulation with oral anticoagulants except for a). prophylactic use of low-dose aspirin for cardioprotection or low dose low molecular weight heparins (LMWH) or b). therapeutic doses of LMWH or specified direct factor Xa inhibitors.
• Administration of a live, attenuated vaccine within 30 days prior to enrollment.

Sponsors & Collaborators

• Exelixis: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (14)

Exelixis Site #8

Los Angeles, California, 90033, United States

Location

Exelixis Site #9

Miami, Florida, 33176, United States

Location

Exelixis Clinical Site #1

Orlando, Florida, 32804, United States

Location

Exelixis Site #11

Tampa, Florida, 33612, United States

Location

Exelixis Site #6

Scarborough, Maine, 04074, United States

Location

Exelixis Site #5

St Louis, Missouri, 63110, United States

Location

Exelixis Clinical Site #3

New Hyde Park, New York, 11776, United States

Location

Exelixis Site #14

New York, New York, 10028, United States

Location

Exelixis Site #13

Shirley, New York, 11987, United States

Location

Exelixis Site #15

The Bronx, New York, 10469, United States

Location

Exelixis Clinical Site #2

Nashville, Tennessee, 37203, United States

Location

Exelixis Clinical Site #16

Salt Lake City, Utah, 84112, United States

Location

Exelixis Site #4

Spokane, Washington, 99208, United States

Location

Exelixis Site #12

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 5, 2024
• Study Start: January 25, 2024
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)