Head and Neck CancerPhase 2NCT05287113
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 Phase 2 study testing Retifanlimab, INCAGN02385 and INCAGN02390 in people with Head and Neck Cancer, run by Incyte Biosciences International Sàrl at 91 sites in 14 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Retifanlimab, INCAGN02385 and INCAGN02390
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 91 sitesin 14 countries
- Study dates
- 14 Nov 2022to 23 Jun 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
91 sites in 14 countries.
91 sites in 14 countries
United States24 sites
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
University of Maryland-Greenebaum Cancer Center
Baltimore, Maryland, 21201
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Virginia - Emily Couric Clinical Cancer Center
Charlottesville, Virginia, 22903
University of Illinois At Chicago
Chicago, Illinois, 60612
Barbara Ann Karmanos Cancer Hospital
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010-9200
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Iowa
Iowa City, Iowa, 52242-1316
City of Hope Orange County
Irvine, California, 92618
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
University of Kansas Hospital Authority
Kansas City, Kansas, 66103
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336
University of California San Diego Medical Center, Moores Cancer Center
La Jolla, California, 92093
City of Hope-Antelope Valley
Lancaster, California, 93534
Innovative Clinical Research Institute
Long Beach, California, 90805
City of Hope National Medical Center
Long Beach, California, 90813
Blessed Health Care
Miami, Florida, 33174
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Huntsman Cancer Institute At University of Utah
Salt Lake City, Utah, 84112
University of California San Francisco Comprehensive Cancer Center
San Francisco, California, 94115
Mayo Clinic Rochester
Scottsdale, Arizona, 85259
Moffitt Cancer Center
Tampa, Florida, 33612-9416
Georgetown University
Washington D.C., District of Columbia, 20057
Spain10 sites
Catalans Institute of Oncology Barcelona
Barcelona, 08916
Ico Girona Hospital Universitari de Girona Dr Josep Trueta
Girona, 17007
Fundacion Jimenez Diaz University Hospital
Madrid, 00034
Hospital Universitario Ramon Y Cajal
Madrid, 28036
Hospital Universitario Quironsalud Madrid
Madrid, 28223
Hospital Regional Universitario Carlos Haya
Málaga, 29010
Complejo Hospitalario de Navarra
Pamplona, 31008
Hospital Universitario Marques de Valdecilla
Santander, 39008
Hospital General Universitario de Valencia
Valencia, 46014
Hospital Universitari I Politecnic La Fe
Valencia, 46026
South Korea8 sites
Pusan National University Yangsan Hospital
Busan, 49241
Chonnam National University Hwasun Hospital
Gwangju, 58128
Cha Bundang Medical Center
Seongnam-si, 13496
Korea University Anam Hospital
Seoul, 02841
Kangbuk Samsung Hospital
Seoul, 03181
Kunkuk University Medical Center
Seoul, 05030
Asan Medical Center
Seoul, 05505
Pusan National University Yangsan Hospital
Yangsan, 50612
Italy7 sites
Fondazione Del Piemonte Per L Oncologia Ircc Candiolo
Candiolo, 10060
Fondazione Irccs Istituto Nazionale Del Tumori Di Milano
Milan, 20133
European Institute of Oncology
Milan, 20141
Istituto Nazionale Tumori Irccs Fondazione Pascale
Naples, 80131
Iov - Istituto Oncologico Veneto Irccs
Padova, 35128
Fondazione Irccs Policlinico San Matteo
Pavia, 27100
Ausl-Irccs Di Reggio Emilia
Reggio Emilia, 42123
Poland6 sites
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka
Bydgoszcz, 85-796
Przychodnia Lekarska Komed Roman Karaszewski
Konin, 62-500
Centrum Onkologii Ziemi Lubelskiej Im. SW. Jana Z Dukli
Lublin, 20-090
Poznan University of Medical Sciences
Poznan, 60-780
Nzoz Provita Prolife Centrum Medyczne
Tomaszów Mazowiecki, 97-200
Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie
Warsaw, 02-781
Portugal6 sites
Hospital de Braga
Braga, 4710-243
Centro Hospitalar Universitario Algarve
Faro, 8000-386
Centro Hospitalar de Lisboa Norte E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035
Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E.
Porto, 4200-072
Centro Hospitalar de Sao Joao Alameda
Porto, 4200-319
Centro Hospitalar de Vila Nova de Gaia/Espinho, Epe-Unidade L
Vila Nova de Gaia, 4434-502
France5 sites
Centre Hospitalier Universitaire de Bordeaux
Bordeaux, 33000
Institut Curie
Paris, 75248
Centre Eugene Marquis
Rennes, 35042
Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
Saint-Herblain, 44805
Icans - Institut de Cancerologie Strasbourg Europe
Strasbourg, 67200
Taiwan5 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 80708
Chang Gung Medical Foundation. Kaohsiung Branch
Kaohsiung City, 83301
China Medical University Hospital
Taichung, 00112
Institutional Review Board Taipei Veterans General Hospital
Taipei, 00112
National Taiwan University Hospital
Taipei, 10002
Georgia4 sites
Jsc Evex Hospitals
K'ut'aisi, 04600
New Hospitals
Tbilisi, 00114
Jsc Evex Corporation-Caraps Medline
Tbilisi, 00159
Ltd Cancer Research Centre
Tbilisi, 0159
Germany4 sites
University of Cologne
Cologne, 50937
Universitatsklinikum Hamburg Eppendorf
Hamburg, 20246
Asklepios Klinik Altona
Hamburg, 22763
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
Mainz, 55131
Greece4 sites
University Hospital of West Attica - Attikon
Chaïdári, 12462
Theagenio Anticancer Hospital
Thessaloniki, 54007
Bioclinic Thessaloniki (Galinos Clinic)
Thessaloniki, 54622
Saint Lukas Clinic
Thessaloniki, 55236
Belgium3 sites
Grand Hospital de Charleroi
Charleroi, 06000
Jessa Ziekenhuis
Hasselt, 03500
Gza Sint Augustinus
Wilrijk, 02610
Canada3 sites
McGill University Health Centre/Glen Site/Cedars Cancer Centre
Montreal, Quebec, H2X 3E4
Chum Hospital Notre Dame
Montreal, Quebec, H2X3E4
McGill University Jewish General Hospital
Montreal, Quebec, H3T 1E2
Netherlands2 sites
The Dutch Cancer Institue
Amsterdam, 1066 CX
Leids Universitair Medisch Centrum (Lumc) (Leiden University Medical Center)
Leiden, 02333
About this study
Official title: 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).
- Conditions
- Head and Neck Cancer
- Being tested
- Retifanlimab, INCAGN02385, INCAGN02390, Placebo
- Keywords
- squamous cell carcinoma of the head and neck (SCCHN), INCAGN02385, INCAGN02390, Retifanlimab, IgG1κ monoclonal antibody, LAG-3, TIM-3, PD-1, PD-L1
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RetifanlimabDrug
Retifanlimab 500mg will be administered intravenously every 4 weeks.
INCAGN02385Drug
INCAGN02385 350mg will be administered intravenously every 2 weeks.
INCAGN02390Drug
INCAGN02390 400 mg will be administered intravenously every 2 weeks.
PlaceboDrug
Placebo will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group 1: Retifanlimab Monotherapy | Experimental | Retifanlimab will be administered intravenously every 4 weeks. Placebos for INCAGN02385 and INCAGN02390 will be administered intravenously every 2 weeks. Receives: Drug: Retifanlimab; Drug: Placebo |
| Treatment Group 2: Retifanlimab + INCAGN02385 | Experimental | Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and Placebo for INCAGN02390 will be administered intravenously every 2 weeks. Receives: Drug: Retifanlimab; Drug: INCAGN02385; Drug: Placebo |
| Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390 | Experimental | 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. Receives: Drug: Retifanlimab; Drug: INCAGN02385; Drug: INCAGN02390 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 738 days
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to approximately 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start14 Nov 2022
- Primary completion14 Mar 2025
- Study completion23 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to 1 of 3 treatment groups.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Biosciences International Sàrl
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05287113
- Sponsor's protocol ID
- INCAGN 2385-203
- Other IDs
- 2023-504270-38-00, 2021-005775-39, 2023
- Status last verified
- Sep 2026
- First submitted
- 11 Mar 2022
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
- Expanded access
- Available