Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors
Conditions
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
Interventions
DRUGzanzalintinib
Specified doses on specified days
DRUGAB521
Specified doses on specified days
BIOLOGICALNivolumab
Specified doses on specified days
Sponsors
Arcus Biosciences, Inc.
Exelixis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. 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. 2. 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. 3. 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. 4. 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. 5. Karnofsky Performance Status (KPS) ≥70%. 6. Screening ambulatory oxygen saturation (SpO2) ≥92%. 7. 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 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. 5. Administration of a live, attenuated vaccine within 30 days prior to enrollment. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Expansion Stage: Progression-free survival (PFS) per RECIST 1.1 as assessed by the Investigator | Up to 24 months |
| Dose-finding Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points | Up to 24 months |
Countries
United States
Outcome results
None listed