Clinical trial NCT06191796: 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)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
Collaborators: name: Arcus Biosciences, Inc.
First posted: 2024-01-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Dose-finding Stage: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to 24 months
measure: Expansion Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator
timeFrame: Up to 24 months
Secondary outcomes:
measure: Dose-finding Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs) and immune-mediated adverse events (imAEs)
timeFrame: Up to 24 months
measure: Dose-finding Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points
timeFrame: Up to 24 months
measure: Dose-finding Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator
timeFrame: Up to 24 months
measure: Expansion Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs), and immune-mediated adverse events (imAEs)
timeFrame: Up to 24 months
measure: Expansion Stage: Duration of response (DOR) per RECIST 1.1 as assessed by the Investigator
timeFrame: Up to 24 months
measure: Expansion Stage: Progression-free survival (PFS) per RECIST 1.1 as assessed by the Investigator
timeFrame: Up to 24 months
measure: Expansion Stage: Overall survival (OS)
timeFrame: Up to 24 months
measure: Expansion Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Exelixis Site #8
state: California
city: Miami
country: United States
facility: Exelixis Site #9
state: Florida
city: Orlando
country: United States
facility: Exelixis Clinical Site #1
state: Florida
city: Tampa
country: United States
facility: Exelixis Site #11
state: Florida
city: Scarborough
country: United States
facility: Exelixis Site #6
state: Maine
city: Saint Louis
country: United States
facility: Exelixis Site #5
state: Missouri
city: Bronx
country: United States
facility: Exelixis Site #15
state: New York
city: New Hyde Park
country: United States
facility: Exelixis Clinical Site #3
state: New York
city: New York
country: United States
facility: Exelixis Site #14
state: New York
city: Shirley
country: United States
facility: Exelixis Site #13
state: New York
city: Nashville
country: United States
facility: Exelixis Clinical Site #2
state: Tennessee
city: Salt Lake City
country: United States
facility: Exelixis Clinical Site #16
state: Utah
city: Spokane
country: United States
facility: Exelixis Site #4
state: Washington
city: Madison
country: United States
facility: Exelixis Site #12
state: Wisconsin
Study officials:
References: