Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
- Conditions
- Recurrent or metastatic head and neck squamous cell carcinomaMedDRA version: 26.1Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506308-24-00
- Lead Sponsor
- Exelixis Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 488
Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy Note: 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. Note: The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx., PD-L1 expression level Combined Positive Score (CPS) = 1 by immunohistochemistry (IHC) testing., Have HPV testing result for oropharyngeal cancer defined as p16 IHC testing., Measurable disease according to RECIST 1.1 determined by the Investigator., Tumor samples (archival or fresh tumor biopsy) are required. If archival tumor 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 older on the day of consent., Eastern Cooperative Oncology Group (ECOG) performance status of 0-1., Adequate organ and marrow function
Nasopharynx, salivary gland or occult primary site (regardless of p16 status), 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., 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 < 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 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with recurrent or metastatic head and neck squamous cell carcinoma;Secondary Objective: To assess safety and tolerability of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with recurrent or metastatic head and neck squamous cell carcinoma, 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 recurrent or metastatic head and neck squamous cell carcinoma, To evaluate the effect of zanzalintinib on specified biomarkers and PK when administered in combination with pembrolizumab in subjects with recurrent or metastatic head and neck squamous cell carcinoma;Primary end point(s): PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by BIRC, Overall Survival (OS)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Incidence and severity of AEs, SAEs, and adverse events of special interest (AESIs);Secondary end point(s):Changes in laboratory parameters and vital signs;Secondary end point(s):PFS per RECIST 1.1 by Investigator;Secondary end point(s):ORR and DOR per RECIST 1.1 by BIRC and Investigator;Secondary end point(s):Plasma concentration of zanzalintinib;Secondary end point(s):Correlation measured between PK of zanzalintinib and selected biomarkers with respect to preliminary safety and efficacy outcomes