study of zanzalintinib (xl092) + pembrolizumab vs pembrolizumab in subjects with pd-l1 positive recurrent or metastatic head and neck squamous cell carcinoma

Conditions: 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.


Eligibility 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) ≥ 1. * 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 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: * 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 \< 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.