Clinical Trial 22712

• Overview

  Study 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

  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.

  Objective:

  Dose Finding Stage Primary: To determine the recommended doses (RDs) of zanzalintinib and AB521 when administered in combination (doublet) in subjects with advanced solid tumors, and in combination plus nivolumab (triplet) in subjects with advanced ccRCC Secondary: To evaluate the safety and tolerability of zanzalintinib administered in combination with AB521 (doublet) in subjects with advanced solid tumors, and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC To evaluate the PK of zanzalintinib and AB521, particularly due to the drug-drug interaction (DDI) when zanzalintinib is administered in combination with AB521(doublet) in subjects with advanced solid tumors, and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC To evaluate preliminary efficacy of zanzalintinib administered in combination with AB521 (doublet) in subjects with advanced solid tumors, and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC Expansion Stage Primary: To evaluate preliminary efficacy of zanzalintinib administered in combination with AB521(doublet), and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC Secondary: To evaluate the safety and tolerability of zanzalintinib administered in combination with AB521 (doublet), and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC To evaluate additional preliminary efficacy of zanzalintinib administered in combination with AB521 (doublet), and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC To evaluate the PK of zanzalintinib and AB521, particularly due to the DDI when zanzalintinib is administered in combination with AB521(doublet), and in combination with AB521 plus nivolumab (triplet) in subjects with advanced ccRCC

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  AB521 (); BMS-936558 (Nivolumab); Nivolumab (Opdivo); Zanzalintinib ()

• Inclusion Criteria

  • Participants with unresectable advanced or metastatic disease or 1L or 2L+ clear cell Renal cell carcinoma.
  • Have not received HIF-2a; 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.

• Exclusion Criteria

  • Participants who have been previously treated with a HIF-2a; 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.
  • Other protocol defined Inclusion/Exclusion criteria may apply.

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