Study of Zanzalintinib in Combination With Immuno-Oncology or Other Agents in Participants With Solid Tumors

Conditions

• Clear Cell Renal Cell Carcinoma (ccRCC)
• Colorectal Cancer (CRC)
• Drug-Drug Interaction (DDI)
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Hepatocellular Carcinoma (HCC)
• Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Non-Clear Cell Renal Cell Carcinoma (nccRCC)
• Non-small Cell Lung Cancer (NSCLC)
• Renal Cell Carcinoma (RCC)
• Solid Tumor
• Urothelial Carcinoma (UC)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Zanzalintinib — DRUG
  Zanzalintinib orally once daily (qd)
• Nivolumab — DRUG
  360 mg intravenous (IV) infusion once every 3 weeks (q3w)
• Ipilimumab — DRUG
  1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
• Nivolumab — DRUG
  3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
• Nivolumab — DRUG
  480 mg IV infusion once every 4 weeks (q4w)
• Nivolumab + Relatlimab — DRUG
  IV administration of nivolumab + relatlimab
• Prednisone — DRUG
  Administered as IV infusion.
• Docetaxel — DRUG
  Administered as oral tablet.
• DDI Probe Cocktail — DRUG
  Midazolam, Warfarin, Omeprazole, and Caffeine administered orally.

Study Details

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) and in combination with docetaxel and prednisone in participants with advanced solid tumors. In addition, the study will evaluate the effect of multiple dose administration of zanzalintinib on the single-dose pharmacokinetics of sensitive CYP3A4, CYP2C9, CYP2C19, or CYP1A2 substrates in participants with advanced solid tumors. In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

Key Dates

First listed

Jan 4, 2022

Start date

Dec 14, 2021

Status verified

Jul 2026

Primary completion

Jan 31, 2027

Completion

Jun 28, 2030

Study Design

Enrollment

1,394 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Zanzalintinib + Nivolumab Dose-Escalation Cohorts
  Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
• Experimental: Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts
  Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
• Experimental: Zanzalintinib + Nivolumab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
• Experimental: Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
• Experimental: Zanzalintinib Single-Agent Expansion Cohorts
• Experimental: Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts
  Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
• Experimental: Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
• Experimental: Zanzalintinib + Docetaxel + Prednisone Dose Expansion Cohort
  Participants with mCRPC, post-androgen receptor pathway inhibitor (post-ARPI), visceral metastases. The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
• Experimental: Zanzalintinib + DDI Probe Substrates Dose Expansion Cohort
  Participants in the DDI Cohort. The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Primary Outcome Measure

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Including Immune-Mediated Adverse Events (imAEs) [ Time Frame: Up to 36 months ]

Central Contacts

• Exelixis Clinical Trials
  1-888-EXELIXIS (888-393-5494)
  [email protected]
• Backup or International
  650-837-7400

Locations (46)

Find similar trials in Phoenix, AZ

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