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)

Exelixis

Status and phase: Terminated; Phase 1

Conditions: Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors

Treatments: Drug: zanzalintinib; Drug: AB521; Biological: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06191796

XL092-009

Details and patient eligibility

About

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

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

25 participants in 4 patient groups

Dose-finding Cohort A: Zanzalintinib + AB521

Experimental group

Description:

Participants with solid tumors will receive zanzalintinib + AB521

Treatment:

Drug: AB521

Drug: zanzalintinib

Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab

Experimental group

Description:

Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab

Treatment:

Biological: Nivolumab

Drug: AB521

Drug: zanzalintinib

Expansion Cohort 1: Zanzalintinib + AB521

Experimental group

Description:

Participants with ccRCC will receive zanzalintinib + AB521

Treatment:

Drug: AB521

Drug: zanzalintinib

Expansion Cohort 2: zanzalintinib + AB521 + nivolumab

Experimental group

Description:

Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab

Treatment:

Biological: Nivolumab

Drug: AB521

Drug: zanzalintinib