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
- Interventions
- Registration Number
- NCT06082167
- Lead Sponsor
- Exelixis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 600
-
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.
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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.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
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Adequate organ and marrow function.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zanzalintinib + Pembrolizumab Pembrolizumab Subjects with R/M HNSCC will receive zanzalintinib + pembrolizumab Zanzalintinib-Matched Placebo + Pembrolizumab Zanzalintinib-matched Placebo Subjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab Zanzalintinib-Matched Placebo + Pembrolizumab Pembrolizumab Subjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab Zanzalintinib + Pembrolizumab Zanzalintinib Subjects with R/M HNSCC will receive zanzalintinib + pembrolizumab
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (168)
Exelixis Clinical Site #2
🇺🇸Fullerton, California, United States
Exelixis Clinical Site #1
🇺🇸Orange City, Florida, United States
Exelixis Clinical Site #163
🇺🇸Tampa, Florida, United States
Exelixis Clinical Site #123
🇺🇸Athens, Georgia, United States
Exelixis Clinical Site #82
🇺🇸Atlanta, Georgia, United States
Exelixis Clinical Site #19
🇺🇸Chicago, Illinois, United States
Exelixis Clinical Site #62
🇺🇸Des Moines, Iowa, United States
Exelixis Clinical Site #100
🇺🇸Iowa City, Iowa, United States
Exelixis Clinical Site #4
🇺🇸Saint Louis, Missouri, United States
Exelixis Clinical Site #148
🇺🇸Lebanon, New Hampshire, United States
Scroll for more (158 remaining)Exelixis Clinical Site #2🇺🇸Fullerton, California, United States