Clinical trial NCT06295731: INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC
Official title: A Phase 2/3, Randomized Study of INBRX-106 Combined With Pembrolizumab Versus Pembrolizumab as First Line Treatment for Patients With Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) Expressing PD-L1 (CPS ≥20) (HexAgon-HN)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
Keywords: OX40 receptor agonist
PD-L1 positive
Pembrolizumab
Immunotherapy
Chemotherapy-free
HNSCC
Head and Neck Cancer
Keytruda
Oropharyngeal cancer
Hypopharyngeal cancer
Laryngeal cancer
Oral cancer
INBRX-106
Lead sponsor: Inhibrx Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2024-03-06
Enrollment: 410
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 seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody INBRX-106 combined with the anti-PD-1 antibody pembrolizumab versus pembrolizumab (+ placebo in phase 3) as first-line treatment for patients with locally advanced recurrent or metastatic head and neck squamous cell carcinoma (R/M HSNSCC) incurable by local therapies, expressing PD-L1 with a combined proportion score (CPS) ≥20.


Eligibility criteria: Inclusion Criteria:

* Has histologically or cytologically confirmed diagnosis of metastatic, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies.
* Has tumor PD-L1 expression of CPS ≥20. Tumor tissue must be provided for PD-L1 biomarker analysis.
* Has human papilloma virus (HPV) testing results for oropharyngeal cancer by p16 immunohistochemistry (IHC) testing.
* Has measurable disease per RECIST 1.1 guidelines.
* Has the primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.
* Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.
* Male and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use a highly effective method of contraception.

Exclusion Criteria:

* Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.
* Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for locally advanced unresectable or metastatic HNSCC.

  * Prior systemic therapy completed \>6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy in the locoregionally advanced disease with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred ≥12 months after its completion.
* Has clinically active central nervous system metastases and/or carcinomatous meningitis.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
* Rapidly progressing disease or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain.
* Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy.

Primary outcomes:
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: up to 6 months
measure: Phase 3: Progression-Free Survival (PFS)
timeFrame: From randomization to first occurrence of progressive disease (PD) or death (up to 4 years)
measure: Phase 3: Overall Survival (OS)
timeFrame: From randomization until death from any cause (up to 4 years)
Secondary outcomes:
measure: Phase 3: Objective Response Rate (ORR)
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: Duration of Response (DOR)
timeFrame: From the first occurrence of a documented objective response to PD or death (up to 4 years)
measure: Clinical Benefit Rate (CBR)
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: Phase 3: Time to Chemotherapy (TTCtx)
timeFrame: From randomization until the start of chemotherapy or death (up to 4 years)
measure: Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: TTCD in physical functioning (PF)
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: TTCD in role functioning (RF)
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: TTCD in Global Health Status/quality of life (GHS/QoL)
timeFrame: From randomization until treatment discontinuation (up to 2 years)
measure: Incidence and severity of Adverse Events (AEs)
timeFrame: Up to approximately 24 months
measure: Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network (LACN)
state: California
city: Sacramento
country: United States
facility: Sutter Health
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: San Diego
country: United States
facility: Medical Oncology Associates of San Diego
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Miami
country: United States
facility: The Oncology Institute of Hope & Innovation
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida, The Maroone Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Billings
country: United States
facility: Intermountain Health, St. Vincent Regional Hospital, Cancer Centers of Montana
state: Montana
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Santa Fe
country: United States
facility: Christus St. Vincent Regional Cancer Center
state: New Mexico
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma University Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Corpus Christi
country: United States
facility: CHRISTUS Spohn Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Jette
country: Belgium
facility: University Hospital Brussels
city: Namur
country: Belgium
facility: Chu Ucl Namur Site De Sainte-Elisabeth
city: Sint-Niklaas
country: Belgium
facility: Vitaz
city: Milan
country: Italy
facility: European Institute of Oncology
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia
state: Kelantan
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
city: Piotrków Trybunalski
country: Poland
facility: Provita Profamilia
city: Craiova
country: Romania
facility: Sc Oncolab Srl
state: Dolj
city: Craiova
country: Romania
facility: Sc Centrul de Oncologie Sf Nectarie Srl
state: Dolj
city: Bucharest
country: Romania
facility: ARENSIA Clinic Oncology Institute Bucharest
city: Cluj-Napoca, Cluj
country: Romania
facility: Arensia Exploratory Medicine S.R.L in collaboration with "Prof. Dr. Ion Chiricuta" Oncology Institute
city: Barcelona
country: Spain
facility: Intituto Catalán de Oncología
state: Catalonia
city: Barcelona
country: Spain
facility: IOB / Institute of Oncology, Hospital Quirónsalud Barcelona
state: Gracia
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
state: Beitou District / R.O.C.
city: Aberdeen
country: United Kingdom
facility: NHS Grampian / Aberdeen Royal Infirmary
Study officials:
affiliation: Inhibrx Biosciences, Inc
name: Clinical Lead
role: STUDY_DIRECTOR
References: