INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC
- Conditions
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- Interventions
- Registration Number
- NCT06295731
- Lead Sponsor
- Inhibrx Biosciences, Inc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 410
- 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.
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Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.
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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.
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Has clinically active central nervous system metastases and/or carcinomatous meningitis.
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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.
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Rapidly progressing disease or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain.
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Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description pembrolizumab monotherapy (+ placebo in phase 3 part) Pembrolizumab Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3) pembrolizumab monotherapy (+ placebo in phase 3 part) INBRX-106 Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3) INBRX-106 plus pembrolizumab INBRX-106 Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3) INBRX-106 plus pembrolizumab Pembrolizumab Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)
- Primary Outcome Measures
Name Time Method Phase 2: Objective Response Rate (ORR) up to 6 months ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) on 2 consecutive occasions ≥4 weeks apart, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Phase 3: Progression-Free Survival (PFS) From randomization to first occurrence of progressive disease (PD) or death (up to 4 years) PFS is defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST v 1.1, or death from any cause (whichever occurs first).
Phase 3: Overall Survival (OS) From randomization until death from any cause (up to 4 years) OS is the time from randomization to death due to any cause
- Secondary Outcome Measures
Name Time Method TTCD in physical functioning (PF) From randomization until treatment discontinuation (up to 2 years) TTCD in PF is defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed PF scale score.
Phase 3: Objective Response Rate (ORR) From randomization until treatment discontinuation (up to 2 years) ORR is defined as the proportion of patients with a CR or PR on 2 consecutive occasions ≥4 weeks apart, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Clinical Benefit Rate (CBR) From randomization until treatment discontinuation (up to 2 years) CBR is defined as the proportion of patients with stable disease (SD) for ≥12 weeks or a CR or PR, as determined by the Investigator according to RECIST v1.1.
Duration of Response (DOR) From the first occurrence of a documented objective response to PD or death (up to 4 years) DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the Investigator according to RECIST v1.1, or death from any cause (whichever occurs first)
TTCD in Global Health Status/quality of life (GHS/QoL) From randomization until treatment discontinuation (up to 2 years) TTCD in GHS/QoL is defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed GHS/QoL scale score.
Incidence and severity of Adverse Events (AEs) Up to approximately 24 months Incidence will be reported as the number of participants with at least one adverse event, with severity determined according to the National Cancer Institute Criteria for Adverse Events, version 5 (NCI CTCAE v 5.0)
Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters Up to approximately 24 months Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure, and temperature. Clinical laboratory parameter include hematology and biochemistry tests over the course of the study.
Phase 3: Time to Chemotherapy (TTCtx) From randomization until the start of chemotherapy or death (up to 4 years) TTCtx is defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first).
Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference From randomization until treatment discontinuation (up to 2 years) TTCD in pain presence and interference is defined as the time from randomization to the first documentation of ≥10-point increase in pain score, as determined using the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) questionnaire
TTCD in role functioning (RF) From randomization until treatment discontinuation (up to 2 years) TTCD in RF is defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed RF scale score.
Trial Locations
- Locations (39)
UC Davis
🇺🇸Sacramento, California, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
University Hospital Brussels
🇧🇪Jette, Belgium
Chu Ucl Namur Site De Sainte-Elisabeth
🇧🇪Namur, Belgium
Vitaz
🇧🇪Sint-Niklaas, Belgium
Hospital Universiti Sains Malaysia
🇲🇾Kubang Kerian, Kelantan, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Sarawak, Malaysia
Institut Kanser Negara
🇲🇾Putrajaya, Malaysia
ARENSIA Clinic Oncology Institute Bucharest
🇷🇴Bucharest, Romania
Arensia Exploratory Medicine S.R.L in collaboration with "Prof. Dr. Ion Chiricuta" Oncology Institute
🇷🇴Cluj-Napoca, Cluj, Romania
IOB / Institute of Oncology, Hospital Quirónsalud Barcelona
🇪🇸Barcelona, Gracia, Spain
Hospital Universitario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Complexo Hospitalario Universitario A Coruña
🇪🇸Coruña, Spain
MD Anderson Cancer Centre
🇪🇸Madrid, Spain
Taipei Veterans General Hospital
🇨🇳Taipei City, Beitou District / R.o.c., Taiwan
NHS Grampian / Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
City of Hope Medical Center
🇺🇸Duarte, California, United States
Los Angeles Cancer Network (LACN)
🇺🇸Los Angeles, California, United States
Sutter Health
🇺🇸Sacramento, California, United States
Medical Oncology Associates of San Diego
🇺🇸San Diego, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
The Oncology Institute of Hope & Innovation
🇺🇸Miami, Florida, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
Cleveland Clinic Florida, The Maroone Cancer Center
🇺🇸Weston, Florida, United States
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Christus St. Vincent Regional Cancer Center
🇺🇸Santa Fe, New Mexico, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University St. Louis
🇺🇸Saint Louis, Missouri, United States
Intermountain Health, St. Vincent Regional Hospital, Cancer Centers of Montana
🇺🇸Billings, Montana, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Oklahoma University Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
CHRISTUS Spohn Cancer Center
🇺🇸Corpus Christi, Texas, United States