Clinical trial NCT06082167: Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-10-13
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
timeFrame: Approximately 33 months after the first subject is randomized
measure: Overall Survival (OS)
timeFrame: Approximately 50 months after the first subject is randomized
Secondary outcomes:
measure: PFS per RECIST 1.1 by Investigator
timeFrame: Approximately 33 months after the first subject is randomized
measure: Objective Response Rate (ORR) per RECIST 1.1 by the BICR and Investigator
timeFrame: Approximately 33 months after the first subject is randomized
measure: Duration of Response (DOR) Per RECIST 1.1 by BICR and Investigator
timeFrame: Approximately 33 months after the first subject is randomized
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Exelixis Clinical Site #2
state: California
city: Orange City
country: United States
facility: Exelixis Clinical Site #1
state: Florida
city: Tampa
country: United States
facility: Exelixis Clinical Site #163
state: Florida
city: Athens
country: United States
facility: Exelixis Clinical Site #123
state: Georgia
city: Atlanta
country: United States
facility: Exelixis Clinical Site #82
state: Georgia
city: Chicago
country: United States
facility: Exelixis Clinical Site #19
state: Illinois
city: Des Moines
country: United States
facility: Exelixis Clinical Site #62
state: Iowa
city: Iowa City
country: United States
facility: Exelixis Clinical Site #100
state: Iowa
city: Saint Louis
country: United States
facility: Exelixis Clinical Site #4
state: Missouri
city: Lebanon
country: United States
facility: Exelixis Clinical Site #148
state: New Hampshire
city: Camden
country: United States
facility: Exelixis Clinical Site #158
state: New Jersey
city: Shirley
country: United States
facility: Exelixis Clinical Site #3
state: New York
city: Durham
country: United States
facility: Exelixis Clinical Site #95
state: North Carolina
city: Wilson
country: United States
facility: Exelixis Clinical Site #117
state: North Carolina
city: Roanoke
country: United States
facility: Exelixis Clinical Site #43
state: Virginia
city: Rosario
country: Argentina
facility: Exelixis Clinical Site #73
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Exelixis Clinical Site #91
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Exelixis Clinical Site # 47
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Exelixis Clinical Site #53
city: Cordoba
country: Argentina
facility: Exelixis Clinical Site #93
city: Córdoba
country: Argentina
facility: Exelixis Clinical Site #64
city: Pergamino
country: Argentina
facility: Exelixis Clinical Site #157
city: Santa Fe
country: Argentina
facility: Exelixis Clinical Site #92
city: Port Macquarie
country: Australia
facility: Exelixis Clinical Site #57
state: New South Wales
city: Adelaide
country: Australia
facility: Exelixis Clinical Site # 46
city: Bedford Park
country: Australia
facility: Exelixis Clinical Site #154
city: Camperdown
country: Australia
facility: Exelixis Clinical Site #137
city: Murdoch
country: Australia
facility: Exelixis Clinical Site #39
city: Linz
country: Austria
facility: Exelixis Clinical Site #156
city: Salzburg
country: Austria
facility: Exelixis Clinical Site #42
city: Vienna
country: Austria
facility: Exelixis Clinical Site #166
city: Bruxelles
country: Belgium
facility: Exelixis Clinical Site #22
city: Charleroi
country: Belgium
facility: Exelixis Clinical Site #106
city: Libramont
country: Belgium
facility: Exelixis Clinical Site #14
city: Sint-Niklaas
country: Belgium
facility: Exelixis Clinical Site #37
city: Passo Fundo
country: Brazil
facility: Exelixis Clinical Site #68
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #90
state: Rio Grande Do Sul
city: Jau
country: Brazil
facility: Exelixis Clinical Site #110
state: Sao Paulo
city: Santo André
country: Brazil
facility: Exelixis Clinical Site #65
state: Sao Paulo
city: São José Do Rio Preto
country: Brazil
facility: Exelixis Clinical Site #83
state: Sao Paulo
city: Barretos
country: Brazil
facility: Exelixis Clinical Site #116
city: Curitiba
country: Brazil
facility: Exelixis Clinical Site #75
city: Curitiba
country: Brazil
facility: Exelixis Clinical Site #101
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #97
city: Recife
country: Brazil
facility: Exelixis Clinical Site #102
city: Rio de Janeiro
country: Brazil
facility: Exelixis Clinical Site #87
city: Sao Paulo
country: Brazil
facility: Exelixis Clinical Site #88
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #76
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #77
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #67
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #98
city: Plovdiv
country: Bulgaria
facility: Exelixis Clinical Site #25
city: Ruse
country: Bulgaria
facility: Exelixis Clinical Site #94
city: Sofia
country: Bulgaria
facility: Exelixis Clinical Site #15
city: Sofia
country: Bulgaria
facility: Exelixis Clinical Site #11
city: Sofia
country: Bulgaria
facility: Exelixis Clinical Site #54
city: Santiago
country: Chile
facility: Exelixis Clinical Site #33
city: Santiago
country: Chile
facility: Exelixis Clinical Site #52
city: Santiago
country: Chile
facility: Exelixis Clinical Site #38
city: Santiago
country: Chile
facility: Exelixis Clinical Site #109
city: Talca
country: Chile
facility: Exelixis Clinical Site #50
city: Valdivia
country: Chile
facility: Exelixis Clinical Site #51
city: Viña Del Mar
country: Chile
facility: Exelixis Clinical Site #40
city: Barranquilla
country: Colombia
facility: Exelixis Clinical Site #96
city: Bogota
country: Colombia
facility: Exelixis Clinical Site #152
city: Floridablanca
country: Colombia
facility: Exelixis Clinical Site #103
city: Pasto
country: Colombia
facility: Exelixis Clinical Site #146
city: Pereira
country: Colombia
facility: Exelixis Clinical Site #149
city: Nový Jičín
country: Czechia
facility: Exelixis Clinical Site #49
city: Olomouc
country: Czechia
facility: Exelixis Clinical Site #58
city: Prague
country: Czechia
facility: Exelixis Clinical Site #34
city: Praha
country: Czechia
facility: Exelixis Clinical Site #151
city: Praha
country: Czechia
facility: Exelixis Clinical Site #48
city: Praha
country: Czechia
facility: Exelixis Clinical Site #36
city: Marseille
country: France
facility: Exelixis Clinical Site #28
state: Bouches-du-Rhône
city: Bordeaux
country: France
facility: Exelixis Clinical Site #16
state: Gironde
city: Rennes
country: France
facility: Exelixis Clinical Site #44
state: Ille Et Vilaine
city: Saint Priest en Jarez
country: France
facility: Exelixis Clinical Site #108
state: Loire
city: Lyon
country: France
facility: Exelixis Clinical Site #70
state: Rhone
city: Le Mans
country: France
facility: Exelixis Clinical Site #107
state: Sarthe
city: Villejuif
country: France
facility: Exelixis Clinical Site #66
state: Val De Marne
city: Dijon Cedex
country: France
facility: Exelixis Clinical Site #144
city: Grenoble Cedex
country: France
facility: Exelixis Clinical Site #141
city: Lille cedex
country: France
facility: Exelixis Clinical Site #140
city: Paris
country: France
facility: Exelixis Clinical Site #26
city: Pierre Benite Cedex
country: France
facility: Exelixis Clinical Site #112
city: Poitiers
country: France
facility: Exelixis Clinical Site #105
city: Giessen
country: Germany
facility: Exelixis Clinical Site #167
city: Athens
country: Greece
facility: Exelixis Clinical Site #155
city: Athens
country: Greece
facility: Exelixis Clinical Site #129
city: Larissa
country: Greece
facility: Exelixis Clinical Site #159
city: Thessaloniki
country: Greece
facility: Exelixis Clinical Site #120
city: Thessaloniki
country: Greece
facility: Exelixis Clinical Site #150
city: Thessaloniki
country: Greece
facility: Exelixis Clinical Site #128
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #125
city: Kecskemet
country: Hungary
facility: Exelixis Clinical Site #99
city: Salgotarjan
country: Hungary
facility: Exelixis Clinical Site #131
city: Szekszard
country: Hungary
facility: Exelixis Clinical Site #147
city: Haifa
country: Israel
facility: Exelixis Clinical Site #132
city: Haifa
country: Israel
facility: Exelixis Clinical Site #85
city: Jerusalem
country: Israel
facility: Exelixis Clinical Site #74
city: Ramat Gan
country: Israel
facility: Exelixis Clinical Site #122
city: Tel Aviv
country: Israel
facility: Exelixis Clinical Site #86
city: Candiolo
country: Italy
facility: Exelixis Clinical Site #21
state: Torino
city: Brescia
country: Italy
facility: Exelixis Clinical Site #35
city: Catania
country: Italy
facility: Exelixis Clinical Site #45
city: Milano
country: Italy
facility: Exelixis Clinical Site #81
city: Milano
country: Italy
facility: Exelixis Clinical Site #55
city: Napoli
country: Italy
facility: Exelixis Clinical Site #18
city: Rome
country: Italy
facility: Exelixis Clinical Site #78
city: Rozzano
country: Italy
facility: Exelixis Clinical Site #124
city: Verona
country: Italy
facility: Exelixis Clinical Site #10
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site #7
state: Gangwon-do
city: Suwon-si
country: Korea, Republic of
facility: Exelixis Clinical Site #30
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Exelixis Clinical Site #17
state: Gyeonggi-do
city: Yangsan
country: Korea, Republic of
facility: Exelixis Clinical Site #9
state: Gyeongsangnam-do
city: Jeonju
country: Korea, Republic of
facility: Exelixis Clinical Site #69
state: Jeollabuk Do
city: Jeonju
country: Korea, Republic of
facility: Exelixis Clinical Site #8
state: Jeollabuk-do
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site #13
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #5
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #63
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #12
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #6
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #29
city: Putrajaya
country: Malaysia
facility: Exelixis Clinical Site #61
state: Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: Exelixis Clinical Site #60
city: Kuala Lumpur
country: Malaysia
facility: Exelixis Clinical Site #72
city: Guadalajara
country: Mexico
facility: Exelixis Clinical Site #114
state: Jalisco
city: San Juan del Rio
country: Mexico
facility: Exelixis Clinical Site #119
state: Queretaro
city: Guadalajara
country: Mexico
facility: Exelixis Clinical Site #168
city: Piotrkow
country: Poland
facility: Exelixis Clinical Site #89
state: Trybunalski
city: Gliwice
country: Poland
facility: Exelixis Clinical Site #139
city: Torun
country: Poland
facility: Exelixis Clinical Site #162
city: Bucuresti
country: Romania
facility: Exelixis Clinical Site #160
city: Cluj-Napoca
country: Romania
facility: Exelixis Clinical Site #24
city: Craiova
country: Romania
facility: Exelixis Clinical Site #20
city: Floreşti
country: Romania
facility: Exelixis Clinical Site #104
city: Ploiesti
country: Romania
facility: Exelixis Clinical Site #127
city: Timisoara
country: Romania
facility: Exelixis Clinical Site #143
city: Košice
country: Slovakia
facility: Exelixis Clinical Site #23
city: Trnava
country: Slovakia
facility: Exelixis Clinical Site #27
city: Zilina
country: Slovakia
facility: Exelixis Clinical Site #121
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #115
city: Girona
country: Spain
facility: Exelixis Clinical Site #113
city: La Coruna
country: Spain
facility: Exelixis Clinical Site #130
city: Madrid
country: Spain
facility: Exelixis Clinical Site #134
city: Madrid
country: Spain
facility: Exelixis Clinical Site #111
city: Madrid
country: Spain
facility: Exelixis Clinical Site #32
city: Madrid
country: Spain
facility: Exelixis Clinical Site #59
city: Madrid
country: Spain
facility: Exelixis Clinical Site #31
city: Pamplona
country: Spain
facility: Exelixis Clinical Site #136
city: Sevilla
country: Spain
facility: Exelixis Clinical Site #126
city: Valencia
country: Spain
facility: Exelixis Clinical Site #153
city: Zaragoza
country: Spain
facility: Exelixis Clinical Site #41
city: Kaohsiung
country: Taiwan
facility: Exelixis Clinical Site #145
city: Taichung
country: Taiwan
facility: Exelixis Clinical Site #164
city: Taipei City
country: Taiwan
facility: Exelixis Clinical Site #142
city: Taipei
country: Taiwan
facility: Exelixis Clinical Site #118
city: Taoyuan
country: Taiwan
facility: Exelixis Clinical Site #165
city: Bangkoknoi
country: Thailand
facility: Exelixis Clinical Site #71
state: Bangkok
city: Chiangmai
country: Thailand
facility: Exelixis Clinical Site #56
state: Chiang Mai
city: Hat Yai
country: Thailand
facility: Exelixis Clinical Site #79
state: Songkhla
city: Bangkok
country: Thailand
facility: Exelixis Clinical Site #80
city: London
country: United Kingdom
facility: Exelixis Clinical Site #135
state: England
city: Romford
country: United Kingdom
facility: Exelixis Clinical Site #84
state: Essex
city: Manchester
country: United Kingdom
facility: Exelixis Clinical Site #138
city: Sutton
country: United Kingdom
facility: Exelixis Clinical Site #133
city: Torquay
country: United Kingdom
facility: Exelixis Clinical Site #161
Study officials:
References: