Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Head and Neck Squamous Cell Carcinoma Clinical Trial

— STELLAR-305  

Official title:

A Phase 2/3, Randomized, Double-Blind, Controlled Study of Zanzalintinib (XL092) in Combination With Pembrolizumab vs Pembrolizumab in First-Line Treatment of Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06082167
• Other study ID #: XL092-305
• Secondary ID: EU CTR: 2023-506
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 30, 2023
• Est. completion date: March 2028

Study information

• Verified date: June 2024
• Source: Exelixis
• Contact: Exelixis Clinical Trials
• Phone: 1-888-EXELIXIS (888-393-5494)
• Email: druginfo[@]exelixis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: March 2028
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 by immunohistochemistry (IHC) testing.
• Have human papilloma virus (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 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.

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Zanzalintinib
Specified doses on specified days
• Zanzalintinib-matched Placebo
Specified doses on specified days

Biological:
• Pembrolizumab
Specified doses on specified days

Locations

Country	Name	City	State
Belgium	Exelixis Clinical Site #22	Bruxelles
Belgium	Exelixis Clinical Site #14	Libramont
Bulgaria	Exelixis Clinical Site #25	Plovdiv
Bulgaria	Exelixis Clinical Site #11	Sofia
Bulgaria	Exelixis Clinical Site #15	Sofia
France	Exelixis Clinical Site #16	Bordeaux	Gironde
Italy	Exelixis Clinical Site #21	Candiolo	Torino
Italy	Exelixis Clinical Site #18	Napoli
Italy	Exelixis Clinical Site #10	Verona
Korea, Republic of	Exelixis Clinical Site #13	Busan
Korea, Republic of	Exelixis Clinical Site #7	Busan	Gangwon-do
Korea, Republic of	Exelixis Clinical Site #8	Jeonju	Jeollabuk-do
Korea, Republic of	Exelixis Clinical Site #12	Seoul
Korea, Republic of	Exelixis Clinical Site #5	Seoul
Korea, Republic of	Exelixis Clinical Site #6	Seoul
Korea, Republic of	Exelixis Clinical Site #17	Suwon	Gyeonggi-do
Korea, Republic of	Exelixis Clinical Site #9	Yangsan	Gyeongsangnam-do
Romania	Exelixis Clinical Site #24	Cluj-Napoca
Romania	Exelixis Clinical Site #20	Craiova
Slovakia	Exelixis Clinical Site #23	Košice
United States	Exelixis Clinical Site #19	Chicago	Illinois
United States	Exelixis Clinical Site #2	Fullerton	California
United States	Exelixis Clinical Site #1	Orange City	Florida
United States	Exelixis Clinical Site #4	Saint Louis	Missouri
United States	Exelixis Clinical Site #3	Shirley	New York

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  France,  Italy,  Korea, Republic of,  Romania,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Radiology Committee (BIRC)	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	Approximately 28 months after the first subject is randomized
Primary	Overall Survival (OS)	Defined as the time from randomization to death due to any cause	Approximately 40 months after the first subject is randomized
Secondary	PFS per RECIST 1.1 by Investigator	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	Approximately 28 months after the first subject is randomized
Secondary	Objective Response Rate (ORR) per RECIST 1.1 by BIRC and Investigator	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	Approximately 28 months after the first subject is randomized
Secondary	Duration of Response (DOR) Per RECIST 1.1 by BIRC and Investigator	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	Approximately 28 months after the first subject is randomized