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)
Phase 1
Recruiting
- Conditions
- Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors
- Interventions
- Registration Number
- NCT06191796
- Lead Sponsor
- Exelixis
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
Inclusion Criteria
- Participants with unresectable advanced or metastatic disease or 1L or 2L+ clear cell Renal cell carcinoma.
- Have not received HIF-2α targeted therapy previously.
- 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.
Key
Exclusion Criteria
- 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 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.
- Administration of a live, attenuated vaccine within 30 days prior to enrollment.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab AB521 Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab Expansion Cohort 1: Zanzalintinib + AB521 AB521 Participants with ccRCC will receive zanzalintinib + AB521 Expansion Cohort 2: zanzalintinib + AB521 + nivolumab AB521 Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab Dose-finding Cohort A: Zanzalintinib + AB521 AB521 Participants with solid tumors will receive zanzalintinib + AB521 Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab Nivolumab Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab Expansion Cohort 2: zanzalintinib + AB521 + nivolumab Nivolumab Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab Dose-finding Cohort A: Zanzalintinib + AB521 zanzalintinib Participants with solid tumors will receive zanzalintinib + AB521 Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab zanzalintinib Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab Expansion Cohort 1: Zanzalintinib + AB521 zanzalintinib Participants with ccRCC will receive zanzalintinib + AB521 Expansion Cohort 2: zanzalintinib + AB521 + nivolumab zanzalintinib Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
- Primary Outcome Measures
Name Time Method 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
Name Time Method Expansion Stage: Overall survival (OS) Up to 24 months 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: 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 Dose-finding Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points 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: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points Up to 24 months
Trial Locations
- Locations (14)
Exelixis Site #8
🇺🇸Los Angeles, California, United States
Exelixis Site #9
🇺🇸Miami, Florida, United States
Exelixis Clinical Site #1
🇺🇸Orlando, Florida, United States
Exelixis Site #11
🇺🇸Tampa, Florida, United States
Exelixis Site #6
🇺🇸Scarborough, Maine, United States
Exelixis Site #5
🇺🇸Saint Louis, Missouri, United States
Exelixis Site #15
🇺🇸Bronx, New York, United States
Exelixis Clinical Site #3
🇺🇸New Hyde Park, New York, United States
Exelixis Site #14
🇺🇸New York, New York, United States
Exelixis Site #13
🇺🇸Shirley, New York, United States
Exelixis Clinical Site #2
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site #16
🇺🇸Salt Lake City, Utah, United States
Exelixis Site #4
🇺🇸Spokane, Washington, United States
Exelixis Site #12
🇺🇸Madison, Wisconsin, United States