Status:

ACTIVE_NOT_RECRUITING

Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Lead Sponsor:

Exelixis

Collaborating Sponsors:

Merck Sharp & Dohme LLC

Conditions:

Head and Neck Squamous Cell Carcinoma

Eligibility:

All Genders

18+ years

Phase:

PHASE2

PHASE3

Brief Summary

This is a multicenter, randomized, double-blind, controlled Phase 2/3 trial of zanzalintinib in combination with pembrolizumab versus zanzalintinib-matched placebo in combination with pembrolizumab in...

Eligibility Criteria

Inclusion

  • Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy.
  • Should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization if given as part of multimodal treatment for locally advanced disease is allowed.
  • The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, and larynx.
  • PD-L1 expression level Combined Positive Score (CPS) ≥ 1.
  • Participants with oropharyngeal cancer must have human papillomavirus (HPV) status from tumor tissue.
  • Measurable disease according to RECIST 1.1 as determined by the Investigator.
  • Tumor samples (archival or fresh tumor biopsy) are required. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.
  • Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Age 18 years (or the legal age of consent in your country, if higher than 18) or older on the day of consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Adequate organ and marrow function.

Exclusion

  • Nasopharynx, salivary gland or occult primary site (regardless of p16 status).
  • Has disease that is suitable for local therapy administered with curative intent.
  • Has received prior therapy with zanzalintinib, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
  • Life expectancy \< 3 months.
  • Had progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
  • Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to randomization.
  • Positive hepatitis B surface antigen (HBsAg) test.
  • Positive hepatitis C virus (HCV) antibody test.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Complete wound healing from major or minor surgery must have occurred at least prior to randomization.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms per electrocardiogram (ECG) within 28 days before randomization.
  • Pregnant or lactating females.
  • Administration of a live, attenuated vaccine within 30 days before randomization.

Key Trial Info

Start Date :

June 7 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

March 1 2029

Estimated Enrollment :

600 Patients enrolled

Trial Details

Trial ID

NCT06082167

Start Date

June 7 2024

End Date

March 1 2029

Last Update

August 17 2025

Active Locations (168)

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Page 1 of 42 (168 locations)

1

Exelixis Clinical Site #2

Fullerton, California, United States, 92835

2

Exelixis Clinical Site #1

Orange City, Florida, United States, 32763

3

Exelixis Clinical Site #163

Tampa, Florida, United States, 33612-9497

4

Exelixis Clinical Site #123

Athens, Georgia, United States, 30607