Head and Neck Squamous Cell Carcinoma
Conditions
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 subjects with programmed death-ligand 1 (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.
Interventions
DRUGZanzalintinib
Specified doses on specified days
DRUGZanzalintinib-matched Placebo
Specified doses on specified days
BIOLOGICALPembrolizumab
Specified doses on specified days
Sponsors
Merck Sharp & Dohme LLC
Exelixis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 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 (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) | Approximately 33 months after the first subject is randomized | Defined as the time from randomization to the earlier of either radiographic progressive disease (PD) per RECIST 1.1 as determined by the BICR or death from any cause |
| Overall Survival (OS) | Approximately 50 months after the first subject is randomized | Defined as the time from randomization to death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS per RECIST 1.1 by Investigator | Approximately 33 months after the first subject is randomized | Defined as the time from randomization to the earlier of either radiographic PD per RECIST 1.1 as determined by the Investigator or death from any cause |
| Objective Response Rate (ORR) per RECIST 1.1 by the BICR and Investigator | Approximately 33 months after the first subject is randomized | Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 as determined by the BICR and Investigator |
| Duration of Response (DOR) Per RECIST 1.1 by BICR and Investigator | Approximately 33 months after the first subject is randomized | Defined as the time from the first documentation of objective response (subsequently confirmed at a visit ≥ 28 days later) to disease progression or death due to any cause |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Colombia, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Malaysia, Mexico, Poland, Romania, Slovakia, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Outcome results
None listed