Efficacy of Retifanlimab, Tuparstobart, and Anti-TIM-3 in PD-L1 Positive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
- Trial ID
- 2023-504270-38-00
- Protocol
- INCAGN 2385-203
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the **efficacy** of the combinations of retifanlimab with INCAGN02385 (TG2) and retifanlimab with INCAGN02385 plus INCAGN02390 (TG3) compared to retifanlimab alone (TG1) in the overall study population. This is clinically relevant as it aims to establish the potential benefits of combination therapies in improving treatment outcomes for participants with PD-L1–positive recurrent/metastatic squamous cell carcinoma of the head and neck.
Secondary objectives include:
- Assessing disease response per RECIST v1.1 in TG2 and TG3 compared with TG1.
- Determining the overall survival (OS) of TG2 and TG3 compared with TG1.
- Evaluating the safety of TG2 and TG3 compared with TG1.
Participants
The clinical trial involves a total of **110 participants** diagnosed with **PD-L1–positive and systemic therapy–naive recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)**. The study population includes both male and female subjects, aged 18 years or older, with an **ECOG performance status** of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants were selected based on their ability to comprehend and willingness to sign an informed consent form, and they must have histologically or cytologically confirmed R/M SCCHN that is not amenable to curative therapy. The trial includes individuals with at least one measurable tumor lesion per RECIST v1.1 and requires the availability of archival tissue for biomarker analysis. The study population is characterized by a diverse age range and includes a vulnerable population. Participants are required to avoid pregnancy or fathering children during the trial. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include PD-L1 positive tumor status and, for those with primary oropharyngeal tumors, documentation of HPV p16 status. Participants who refuse potentially curative salvage surgery for recurrent disease are excluded from the study.
Plans and Procedures
The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the efficacy of **retifanlimab** in combination with **INCAGN02385** and **INCAGN02390** as a first-line treatment for participants with PD-L1-positive recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The trial is structured to compare the therapeutic effects of the combination treatments against retifanlimab alone. The study is expected to span approximately 24 months, with an estimated end date in December 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, tumor status, and performance status. Following successful screening, participants will be randomized into one of the treatment groups. The trial includes regular follow-up visits to monitor treatment efficacy and safety, assess disease progression, and manage any adverse events. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the primary endpoint of progression-free survival (PFS) and secondary endpoints such as objective response and overall survival (OS).
The expected length of participant involvement is up to 24 months, contingent upon disease progression or the occurrence of adverse events that may necessitate early termination from the study. Conditions leading to early withdrawal include significant disease progression, unacceptable toxicity, or withdrawal of consent. Participants are required to comply with study protocols, including regular visits and assessments, to ensure the integrity of the trial data.
Treatment
The clinical trial involves the administration of three experimental medications, each formulated as a **solution for infusion**. The first medication, **Retifanlimab (INCMGA00012)**, is a biological product of biotechnological origin, developed by Incyte Corporation. It is administered intravenously with a maximum daily dose of 500 mg. The treatment period for Retifanlimab is up to 24 weeks. The active substance, retifanlimab, is a protein of other origin, specifically designed for this study.
The second experimental medication is **INCAGN02385**, containing the active substance **Tuparstobart**. This medication is also a solution for infusion, administered intravenously. The maximum daily dose for INCAGN02385 is 350 mg, with a treatment duration of up to 24 weeks. The product is of biological/biotechnological origin and is developed by Incyte Biosciences International Sàrl. Tuparstobart is a protein of other origin, contributing to the therapeutic regimen of the trial.
The third medication, **INCAGN02390**, is formulated with a **human IgG1k monoclonal antibody against TIM-3**. Like the other medications, it is a solution for infusion administered intravenously. The maximum daily dose is 400 mg, and the treatment period extends up to 24 weeks. This product is also of biological/biotechnological origin, developed by Incyte Corporation. The active substance is a protein of other origin, specifically targeting TIM-3 in the study.
All three medications are administered as part of a randomized, double-blind, multicenter, Phase 2 study. The trial aims to evaluate the efficacy of these combinations as first-line treatment in participants with PD-L1–positive recurrent/metastatic squamous cell carcinoma of the head and neck. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the interval between the date of randomization and the earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death due to any cause. Secondary endpoints include objective response, defined as having a complete response (CR) or partial response (PR), determined based on investigator assessment per RECIST v1.1. Duration of Response (DOR) is defined as the time from the earliest date of disease response (CR or PR) until the earliest date of disease progression, or death from any cause if occurring sooner than progression. Disease control is defined as having CR, PR, or stable disease (SD) for at least 6 months as the best response, based on investigator assessment per RECIST v1.1. Overall Survival (OS) is defined as the interval between the date of randomization until death due to any cause.
Adverse events (AEs) will be assessed in body systems with symptoms, through physical examinations, changes in vital signs and ECGs, and through clinical laboratory blood sample evaluations. The impact on study treatment will be assessed by treatment interruptions, dose delays, and withdrawal of study treatment due to AEs. The efficacy parameters will be measured and collected at specified timepoints throughout the trial, with analysis conducted according to the predefined criteria. The trial aims to determine the efficacy of the combinations of retifanlimab with INCAGN02385 and INCAGN02390 compared with retifanlimab alone in participants with PD-L1-positive recurrent/metastatic squamous cell carcinoma of the head and neck.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to comprehend and willingness to sign a written ICF for the study.
- Age 18 years or older (or as applicable per local country requirements), inclusive at the time of signing the ICF.
- Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy). Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible.
- PD-L1 positive tumor status defined by CPS ≥ 1 per central laboratory determination.
- For participants with primary oropharyngeal tumors, documentation of HPV p16 status (positive or negative) 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 based on the criteria
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 (in any disease setting) 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 (this includes curative radiation to the thorax or systemic anticancer therapies).
- Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.
- Less than 3-month life expectancy (based on investigator judgment).
- Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy (with exceptions for anemia not requiring transfusion support, fatigue, or any grade of alopecia).
- 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.
- Participants with laboratory values at screening defined in Table 7.
- Has known active HBV or HCV infection, or risk of reactivation of HBV or HCV, defined as follows (testing must be performed to determine eligibility): a. Active HBV infection is defined by positive HBsAg and positive total anti-HBc results. Note: If HBsAg is negative AND HBcAb and/or HBsAb is positive, HBV-DNA will be evaluated; when HBV-DNA is negative, the participant can then be enrolled with close monitoring of HBV activities. b. Active HCV is defined as a positive HCV antibody result and quantitative HCV-RNA results greater than the lower limits of detection of the assay. Note: Participants positive for HCV antibody will be eligible if they are negative for HCV-RNA. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable.
- Participants who are known to be HIV-positive, unless all of the following criteria are met: a. CD4+ count ≥ 300/μL. b. Undetectable viral load. c. Receiving antiretroviral therapy that is not a potential risk for a drug-drug interaction with the assigned study drug.
- Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of the first dose of study treatment with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has completed treatment > 2 years before randomization in this study and has been disease-free since completion of treatment with curative intent.
- Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
- Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
- Active infections (besides those described in Exclusion Criteria 11 and 12) requiring systemic antibiotics or antifungal or antiviral treatment (within 14 days before first dose of study treatment).
- Evidence of interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
- History of organ transplant, including allogeneic stem cell transplantation.
- Receiving probiotics as of the first dose of study treatment.
- History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 460 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is > 460 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is ≤ 460 milliseconds
- Has had a significant cardiac event within 6 months before the first dose of study treatment, including New York Heart Association Class III/IV, acute myocardial infarction (including severe/unstable angina), cardiomyopathy, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, critical conduction delay, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
- Has received a live vaccine within 30 days of planned start of study treatment.
- Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
- Known allergy or hypersensitivity to any component of either retifanlimab, INCAGN02385, or INCAGN02390 study drug formulation (including excipients and additives).
- Women who are pregnant or breastfeeding.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
- The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 30 Sept 2022 | 6 |
 Greece | Not Recruiting | 30 Sept 2022 | 18 |
 Italy | Not Recruiting | 30 Sept 2022 | 11 |
 Portugal | Not Recruiting | 30 Sept 2022 | 11 |
 Spain | Not Recruiting | 30 Sept 2022 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
INCAGN02385 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 350 | 24 | PRD6569350 |
RetifanlimabINCMGA00012 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 500 | 24 | PRD6569529 |
INCAGN02390 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 400 | 24 | PRD10013206 |