STELLAR-305: Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Study Details
Study Description
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 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Zanzalintinib + Pembrolizumab Subjects with R/M HNSCC will receive zanzalintinib + pembrolizumab |
Drug: Zanzalintinib
Specified doses on specified days
Other Names:
Biological: Pembrolizumab
Specified doses on specified days
Other Names:
|
| Placebo Comparator: Zanzalintinib-Matched Placebo + Pembrolizumab Subjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab |
Drug: Zanzalintinib-matched Placebo
Specified doses on specified days
Other Names:
Biological: Pembrolizumab
Specified doses on specified days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Radiology Committee (BIRC) [Approximately 28 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 BIRC or death from any cause
- Overall Survival (OS) [Approximately 40 months after the first subject is randomized]
Defined as the time from randomization to death due to any cause
Secondary Outcome Measures
- PFS per RECIST 1.1 by Investigator [Approximately 28 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 BIRC and Investigator [Approximately 28 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 BIRC and Investigator
- Duration of Response (DOR) Per RECIST 1.1 by BIRC and Investigator [Approximately 28 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy.
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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.
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The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, and larynx.
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PD-L1 expression level Combined Positive Score (CPS) ≥ 1 by immunohistochemistry (IHC) testing.
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Have human papilloma virus (HPV) testing result for oropharyngeal cancer defined as p16 IHC testing.
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Measurable disease according to RECIST 1.1 determined by the Investigator.
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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.
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Age 18 years 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.
Exclusion Criteria:
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Nasopharynx, salivary gland or occult primary site (regardless of p16 status).
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Has disease that is suitable for local therapy administered with curative intent.
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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).
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Life expectancy < 3 months.
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Had progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
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Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
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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.
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Positive hepatitis B surface antigen (HBsAg) test.
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Positive hepatitis C virus (HCV) antibody test.
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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.
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Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 28 days before randomization.
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Pregnant or lactating females.
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Administration of a live, attenuated vaccine within 30 days before randomization.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Exelixis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XL092-305
- EU CTR: 2023-506308-24-00