Clinical Trial 23298

• Overview

  Study Title:

  A Phase 2/3, Randomized, Double-Blind, Controlled Study of Zanzalintinib (XL092) in Combination with Pembrolizumab Vs Pembrolizumab in the First-Line Treatment Of Subjects with PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

  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 subjects with PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) incurable by local therapies who have not received prior systemic therapy for recurrent or metastatic disease.

  Objective:

  Primary Objective: * To compare the efficacy of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with R/M HNSCC Secondary Objectives: * To assess safety and tolerability of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with R/M HNSCC * To compare additional efficacy outcomes (PFS, ORR, and duration of response [DOR] by Investigator and ORR and DOR by BIRC) for zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with R/M HNSCC * To evaluate the effect of zanzalintinib on specified biomarkers and PK when administered in combination with pembrolizumab in subjects with R/M HNSCC

• Treatments

  Therapies:

  Immunotherapy; Tyrosine Kinase Inhibitor

  Medications:

  Pembrolizumab (Keytruda); Placebo (); Zanzalintinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy. Subjects 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) of 1 or more.
  • Subjects with oropharyngeal cancer must have 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 or less 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 Criteria

  Exclusion Criteria:
  • 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 (eg, CTLA-4, OX-40, CD137).
  • Life expectancy > 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.

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