INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC (HexAgon-HN)

May 6, 2026 updated by: Inhibrx Biosciences, Inc

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

410

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
  • Belgium
      • Jette, Belgium, 1090
        • University Hospital Brussels
      • Namur, Belgium, 5000
        • Chu Ucl Namur Site De Sainte-Elisabeth
      • Sint-Niklaas, Belgium, 9100
        • Vitaz
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • Antwerp University Hospital
  • Bulgaria
      • Panagyurishte, Bulgaria, 4500
        • Multiprofile Hospital for Active Treatment - "Uni Hospital" Ltd, Medical Oncology Dept
      • Plovdiv, Bulgaria, 4004
        • Complex Oncological Center Plovdiv EOOD Dept of Med Oncology and Oncological Diseases in Hematology
      • Sofia, Bulgaria, 1527
        • Uni Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD Clinic of Medical Oncology
      • Sofia, Bulgaria, 1618
        • Multiprofile Hospital for Active Treatment Sveta Sofia, Department of Medical Oncology
  • France
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Lille, France, 59000
        • Cenre Oscar Lambret
      • Lyon, France, 69008
        • Centre Leon Berard
    • Epagny Metz Tessy
      • Annecy, Epagny Metz Tessy, France, 74370
        • Ch Annecy Genevois
    • Moselle
      • Metz, Moselle, France, 57000
        • UNEOS-Hopital R.SCHUMAN
  • Italy
      • Milan, Italy, 20141
        • European Institute of Oncology
      • Milan, Italy, 20133
        • Istituto Nazionale Tumori IRCCS - (National Cancer Institute)
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
    • Naples
      • Naples, Naples, Italy, 80131
        • Istituto Nazionale Tumori IRCCS - Fondazione Giovanni Pascale (National Cancer Institute)
  • Malaysia
      • Petaling Jaya, Malaysia, 46050
        • Beacon Hospital
      • Putrajaya, Malaysia, 62250
        • Institut Kanser Negara
    • Kelantan
      • Kubang Kerian, Kelantan, Malaysia, 16150
        • Hospital Universiti Sains Malaysia
    • Kuala Lumpur
      • Cheras, Kuala Lumpur, Malaysia, 56000
        • Hospital Canselor Tuanku Muhriz (HCTM) UKM
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Sarawak General Hospital
    • Selangor
      • Petaling Jaya, Selangor, Malaysia, 47810
        • Thomson Hospital Kota Damansara
  • Poland
      • Gliwice, Poland, 44-102
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział w Gliwicach
      • Konin, Poland, 62-500
        • Przychodnia Lekarska KOMED
      • Piotrkow Trybunalski, Poland, 97-300
        • Provita Profamilia
  • Romania
      • Bucharest, Romania, 022328
        • ARENSIA Clinic Oncology Institute Bucharest
      • Cluj-Napoca, Cluj, Romania, 400015
        • Arensia Exploratory Medicine S.R.L in collaboration with "Prof. Dr. Ion Chiricuta" Oncology Institute
    • Dolj
      • Craiova, Dolj, Romania, 200385
        • Sc Oncolab Srl
      • Craiova, Dolj, Romania, 200745
        • Sc Centrul de Oncologie Sf Nectarie Srl
  • South Korea
      • Daegu, South Korea, 42601
        • Keimyung University Dongsan Hospital of Korea
      • Seoul, South Korea, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea, 02841
        • Korea University Anam Hospital
      • Seoul, South Korea, 08308
        • Korea University Guro Hospital
      • Seoul, South Korea, 01812
        • Korea Cancer Center Hospital
    • Eunpyeong-gu
      • Seoul, Eunpyeong-gu, South Korea, 03312
        • The Catholic University of Korea, Eunpyeong St. Mary's Hospital
    • Gyeongsangnam-do
      • Yangsan, Gyeongsangnam-do, South Korea, 50612
        • Pusan National University Yangsan Hospital
    • Incheon
      • Seoul, Incheon, South Korea, 21565
        • Gachon University Gil Medical Center of Korea
  • Spain
      • A Coruña, Spain, 15006
        • Complexo Hospitalario Universitario A Coruña
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Madrid, Spain, 28033
        • Md Anderson Cancer Centre
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
    • A Coruña
      • Santiago, A Coruña, Spain, 15706
        • Hospital Clinico Universitario de Santiago de Compostela
    • Catalonia
      • Barcelona, Catalonia, Spain, 08908
        • Intituto Catalán de Oncología
    • Gracia
      • Barcelona, Gracia, Spain, 08023
        • IOB / Institute of Oncology, Hospital Quirónsalud Barcelona
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Hospital Universitario de Navarra
    • Retiro
      • Madrid, Retiro, Spain, 28007
        • Hospital Universitario Gregorio Maranon
  • Taiwan
      • Changhua, Taiwan, 500
        • Changhua Christian Medical Foundation Changhua Christian Hospital
      • Kaohsiung City, Taiwan, 80756
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100226
        • National Taiwan University Hospital
    • Beitou District / R.o.c.
      • Taipei, Beitou District / R.o.c., Taiwan, 11217
        • Taipei Veterans General Hospital
    • China
      • Taichung, China, Taiwan, 407219
        • Taichung Veterans General Hospital
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZN
        • NHS Grampian / Aberdeen Royal Infirmary
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital
      • Manchester, United Kingdom, M204BX
        • The Christie NHS Foundation Trust
      • Norwich, United Kingdom, NR47UY
        • Norwich and Norfolk University Hospital
    • London
      • Chelsea, London, United Kingdom, SW36JJ
        • The Royal Marsden NHS Foundation Trust, Chelsea
    • Middlesex
      • Northwood, Middlesex, United Kingdom, HA6 2RN
        • Mount Vernon Cancer Centre
    • Northumbria
      • Newcastle upon Tyne, Northumbria, United Kingdom, NE7 7DN
        • The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Northern Centre for Cancer Care, Freeman Hospital
    • Surrey
      • Sutton, Surrey, United Kingdom, SM25PT
        • The Royal Marsden NHS Foundation Trust, Sutton
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
      • Los Angeles, California, United States, 91204
        • Los Angeles Cancer Network (LACN)
      • Sacramento, California, United States, 95817
        • UC Davis
      • San Diego, California, United States, 92123
        • Medical Oncology Associates of San Diego
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • ChristianaCare Health Services
    • Florida
      • Gainesville, Florida, United States, 32608
        • University of Florida UF Health Cancer Center
      • Miami, Florida, United States, 33169
        • The Oncology Institute of Hope & Innovation
      • Orange City, Florida, United States, 32763
        • Mid Florida Hematology and Oncology Center
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida, The Maroone Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University St. Louis
    • Montana
      • Billings, Montana, United States, 59102
        • Intermountain Health, St. Vincent Regional Hospital, Cancer Centers of Montana
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • CHRISTUS St. Vincent Regional Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • UNC Lineberger Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Texas
      • Corpus Christi, Texas, United States, 78404
        • CHRISTUS Spohn Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: INBRX-106 plus pembrolizumab
Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)
Drug: INBRX-106
INBRX-106 by intravenous (IV) infusion, given every 3 weeks (QW3)
Other Names:
  • Hexavalent OX40 agonist antibody
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given every 3 weeks (QW3)
Other Names:
  • Keytruda
Active Comparator: pembrolizumab monotherapy (+ placebo in phase 3 part)
Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3)
Drug: INBRX-106
INBRX-106 by intravenous (IV) infusion, given every 3 weeks (QW3)
Other Names:
  • Hexavalent OX40 agonist antibody
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given every 3 weeks (QW3)
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2: Objective Response Rate (ORR)
Time Frame: 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)
up to 6 months
Phase 3: Progression-Free Survival (PFS)
Time Frame: 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).
From randomization to first occurrence of progressive disease (PD) or death (up to 4 years)
Phase 3: Overall Survival (OS)
Time Frame: From randomization until death from any cause (up to 4 years)
OS is the time from randomization to death due to any cause
From randomization until death from any cause (up to 4 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 3: Objective Response Rate (ORR)
Time Frame: 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)
From randomization until treatment discontinuation (up to 2 years)
Duration of Response (DOR)
Time Frame: 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)
From the first occurrence of a documented objective response to PD or death (up to 4 years)
Clinical Benefit Rate (CBR)
Time Frame: 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.
From randomization until treatment discontinuation (up to 2 years)
Phase 3: Time to Chemotherapy (TTCtx)
Time Frame: 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).
From randomization until the start of chemotherapy or death (up to 4 years)
Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference
Time Frame: 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
From randomization until treatment discontinuation (up to 2 years)
TTCD in physical functioning (PF)
Time Frame: 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.
From randomization until treatment discontinuation (up to 2 years)
TTCD in role functioning (RF)
Time Frame: 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.
From randomization until treatment discontinuation (up to 2 years)
TTCD in Global Health Status/quality of life (GHS/QoL)
Time Frame: 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.
From randomization until treatment discontinuation (up to 2 years)
Incidence and severity of Adverse Events (AEs)
Time Frame: 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)
Up to approximately 24 months
Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters
Time Frame: 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.
Up to approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inhibrx Biosciences, Inc

Investigators

  • Study Director: Clinical Lead, Inhibrx Biosciences, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2024

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

February 22, 2024

First Submitted That Met QC Criteria

February 28, 2024

First Posted (Actual)

March 6, 2024

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INBRX106-01-201
  • EU CT (Other Identifier: 2024-512981-33-00)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Squamous Cell Carcinoma (HNSCC)

Clinical Trials on INBRX-106

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Germany

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe