Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

A Randomized, Double-Blind, Multicenter, Phase 2 Study of Retifanlimab in Combination With INCAGN02385 (Anti-LAG-3) and INCAGN02390 (Anti-TIM-3) as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

The purpose of this study is to evaluate the safety and efficacy of the combination of retifanlimab plus INCAGN02385 and retifanlimab plus INCAGN02385 and INCAGN02390 compared with retifanlimab alone as first-line treatment in PD-L1-positive and systemic therapy-naive recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Retifanlimab; Drug: Placebo; Drug: INCAGN02385; Drug: INCAGN02390

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Charleroi, Belgium, 06000
    • Grand hospital de Charleroi
  • Hasselt, Belgium, 03500
    • Jessa Ziekenhuis
  • Wilrijk, Belgium, 02610
    • Gza Sint Augustinus
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University Jewish General Hospital
    • Montreal, Quebec, Canada, H2X 3E4
      • McGill University Health Centre/Glen Site/Cedars Cancer Centre
    • Montreal, Quebec, Canada, H2X3E4
      • Chum Hospital Notre Dame
• France
  • Bordeaux, France, 33000
    • Centre Hospitalier Universitaire de Bordeaux
  • Paris, France, 75248
    • Institut Curie
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Saint-Herblain, France, 44805
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Strasbourg, France, 67200
    • ICANS - Institut de cancérologie Strasbourg Europe
• Georgia
  • K'ut'aisi, Georgia, 04600
    • JSC Evex Hospitals
  • Tbilisi, Georgia, 00114
    • New Hospitals
  • Tbilisi, Georgia, 00159
    • Jsc Evex Corporation-Caraps Medline
  • Tbilisi, Georgia, 0159
    • LTD Cancer Research Centre
• Germany
  • Cologne, Germany, 50937
    • University of Cologne
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg Eppendorf
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
• Greece
  • Chaïdári, Greece, 12462
    • University Hospital of West Attica - Attikon
  • Thessaloniki, Greece, 54007
    • Theagenio Anticancer Hospital
  • Thessaloniki, Greece, 54622
    • Bioclinic Thessaloniki (Galinos clinic)
  • Thessaloniki, Greece, 55236
    • Saint Lukas Clinic
• Italy
  • Candiolo, Italy, 10060
    • Fondazione Del Piemonte Per L Oncologia Ircc Candiolo
  • Milan, Italy, 20141
    • European Institute of Oncology
  • Milan, Italy, 20133
    • Fondazione Irccs Istituto Nazionale Del Tumori Di Milano
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Padua, Italy, 35128
    • Iov - Istituto Oncologico Veneto Irccs
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Reggio Emilia, Italy, 42123
    • AUSL-IRCCS di Reggio Emilia
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • The Dutch Cancer Institue
  • Leiden, Netherlands, 02333
    • Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka
  • Konin, Poland, 62-500
    • Przychodnia Lekarska KOMED Roman Karaszewski
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
  • Poznan, Poland, 60-780
    • Poznan University of Medical Sciences
  • Tomaszów Mazowiecki, Poland, 97-200
    • Nzoz Provita Prolife Centrum Medyczne
  • Warsaw, Poland, 02-781
    • Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Faro, Portugal, 8000-386
    • Centro Hospitalar Universitario Algarve
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte E.P.E. - Hospital de Santa Maria
  • Porto, Portugal, 4200-072
    • Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de Sao Joao Alameda
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia/Espinho, Epe-Unidade L
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Yangsan Hospital
  • Gwangju, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seongnam-si, South Korea, 13496
    • CHA Bundang Medical Center
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 05030
    • Kunkuk University Medical Center
  • Yangsan, South Korea, 50612
    • Pusan National University Yangsan Hospital
• Spain
  • Barcelona, Spain, 08916
    • Catalans Institute of Oncology Barcelona
  • Girona, Spain, 17007
    • Ico Girona Hospital Universitari de Girona Dr Josep Trueta
  • Madrid, Spain, 28223
    • Hospital Universitario Quirónsalud Madrid
  • Madrid, Spain, 00034
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28036
    • Hospital Universitario Ramon y Cajal
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya
  • Pamplona, Spain, 31008
    • Complejo Hospitalario de Navarra
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• Taiwan
  • Kaohsiung City, Taiwan, 80708
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Medical Foundation. Kaohsiung Branch
  • Taichung, Taiwan, 00112
    • China Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 00112
    • Institutional Review Board Taipei Veterans General Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Rochester
  • California
    • Duarte, California, United States, 91010-9200
      • City of Hope National Medical Center
    • Irvine, California, United States, 92618
      • City of Hope Orange County
    • La Jolla, California, United States, 92093
      • University of California San Diego Medical Center, Moores Cancer Center
    • Lancaster, California, United States, 93534
      • City of Hope-Antelope Valley
    • Long Beach, California, United States, 90813
      • City of Hope National Medical Center
    • Long Beach, California, United States, 90805
      • Innovative Clinical Research Institute
    • San Francisco, California, United States, 94115
      • University of California San Francisco Comprehensive Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33174
      • Blessed Health Care
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242-1316
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • University of Kansas Hospital Authority
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland-Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Cancer Center
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia - Emily Couric Clinical Cancer Center
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent. Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible.
• Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
• Participants must not have received prior systemic therapy for R/M SCCHN.
• PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratory determination.
• For participants with primary oropharyngeal tumors, documentation of HPV p16 status based on local institutional standard is required. HPV p16 status is not required for other eligible SCCHN primary tumor sites.
• Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
• Availability of archival tissue for biomarker analysis from a core or excisional biopsy or willingness to undergo a fresh biopsy.
• ECOG performance status of 0 or 1.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Progressive or recurrent disease within 6 months of the last dose of systemic treatment for locally advanced SCCHN. Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN or any other malignancy.
• Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment.
• Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.
• Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivary and are excluded.
• Less than 3-month life expectancy.
• Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.
• Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
• Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months before the first dose of study treatment.
• Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been < 4 weeks since radiation therapy was delivered to the CNS.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1: Retifanlimab Monotherapy; Retifanlimab will be administered intravenously every 4 weeks. Placebos for INCAGN02385 and INCAGN02390 will be administered intravenously every 2 weeks.	Drug: Retifanlimab; Retifanlimab 500mg will be administered intravenously every 4 weeks.; Drug: Placebo; Placebo will be administered intravenously.
Experimental: Treatment Group 2: Retifanlimab + INCAGN02385; Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and Placebo for INCAGN02390 will be administered intravenously every 2 weeks.	Drug: Retifanlimab; Retifanlimab 500mg will be administered intravenously every 4 weeks.; Drug: Placebo; Placebo will be administered intravenously.; Drug: INCAGN02385; INCAGN02385 350mg will be administered intravenously every 2 weeks.
Experimental: Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390; Retifanlimab plus INCAGN02385 and INCAGN02390 will be administered intravenously. Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and INCAGN02390 will be administered every 2 weeks.	Drug: Retifanlimab; Retifanlimab 500mg will be administered intravenously every 4 weeks.; Drug: INCAGN02385; INCAGN02385 350mg will be administered intravenously every 2 weeks.; Drug: INCAGN02390; INCAGN02390 400 mg will be administered intravenously every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progeression-free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of the first documented progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death due to any cause, whichever occurred first.	up to 738 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response	Objective response was defined as having a complete response (CR) or partial response (PR), determined based on investigator assessment per RECIST v1.1, recorded post-baseline before and including the first progressive disease, and before new anticancer therapy. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.	up to approximately 44 months
Duration of Response (DOR)	DOR was defined as the time from earliest date of disease response (CR or PR) until the earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death from any cause if occurring sooner than progression.	up to approximately 44 months
Disease Control	Disease control was defined as having CR, PR, or stable disease (SD) as best response on or after Day 180, based on investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.	up to approximately 44 months
Overall Survival	Overall survival was defined as the time from the date of randomization to the date of death due to any cause.	up to approximately 44 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 90 days of the last administration of study drug.	up to approximately 44 months
Number of Participants With TEAEs Leading to Treatment Interruption, Dose Delay, and Withdrawal of Study Treatment	AEs were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 90 days of the last administration of study drug.	up to approximately 44 months

Collaborators and Investigators

• Sponsor: Incyte Biosciences International Sàrl

Publications and helpful links

Helpful Links

• Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Actual): March 14, 2025
• Study Completion (Estimated): July 10, 2026

Study Registration Dates

• First Submitted: March 11, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; INCAGN02385; INCAGN02390; LAG-3; TIM-3; Retifanlimab; squamous cell carcinoma of the head and neck (SCCHN); IgG1κ monoclonal antibody
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
• Other Study ID Numbers: INCAGN 2385-203; 2021-005775-39 (EudraCT Number); 2023-504270-38-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No