INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
- Conditions
- Advanced MalignanciesMetastatic Head and Neck Squamous Cell CarcinomaRecurrent Head and Neck Squamous Cell Carcinoma
- Interventions
- Biological: INCAGN01876Biological: retifanlimab
- Registration Number
- NCT05359692
- Lead Sponsor
- Incyte Biosciences International Sàrl
- Brief Summary
The purpose of this study is to determine the safety, tolerability, efficacy, PK and pharmacodynamics of INCAGN01876 when given in combination with retifanlimab. The study will consist of 2 parts: a safety lead-in part (Part 1) followed by a dose expansion part (Part 2).
- Detailed Description
The purpose of this study is to determine the safety, tolerability, efficacy, PK and pharmacodynamics of INCAGN01876 when given in combination with retifanlimab in participants with GITR expression in recurrent or metastatic HNSCC who have progressed on or after prior systemic therapy including anti-PD-(L)1 therapy. The study will consist of 2 parts: a safety lead-in part (Part 1) followed by a dose expansion part (Part 2)
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, hypopharynx, or larynx), that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Participants with squamous cell carcinomas of the nasopharynx, salivary gland, or nonsquamous cell histology are excluded.
- Documented progression on or after PD-(L)1 inhibitor alone or in combination with platinum-based chemotherapy for recurrent or metastatic HNSCC. Exception: Treatment Group B (Part 2, expansion): PD-(L)1-naïve.
- ECOG performance status of 0 to 1.
- Measurable disease based on RECIST v1.1.
- Mandatory pre-treatment and on-treatment tumor biopsies.
- GITR-positive tumor confirmed by central laboratory before study treatment start.
- Willingness to avoid pregnancy or fathering children.
- Have received chemotherapy, targeted small molecule therapy or curative radiation within 21 days of first dose of study drug; prior mAB for anticancer therapy other within 28 days of first dose of study drug; or investigational study drugs or devices within 28 days or five half-lives prior to enrollment unless approved by medical monitor.
- Prior treatment with any TNF Super Family agonist therapy.
- Have not recovered to ≤ Grade 1 from toxic effects of prior therapy.
- Laboratory and medical history parameters not within the Protocol-defined range before the first administration of study treatment.
Known active HBV or HCV, or Known to be seropositive for HIV.
- Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Known active infections requiring systemic treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Cohort 2 INCAGN01876 INCAGN01876 Q2W with retifanlimab Q4W. Part 1: Cohort 2 retifanlimab INCAGN01876 Q2W with retifanlimab Q4W. Part 2 (Expansion): Treatment Group B retifanlimab INCAGN01876 and retifanlimab combination in participants who are naive to anti-PD-(L)1 therapy. Part 2 (Expansion): Treatment Group A retifanlimab INCAGN01876 and retifanlimab combination in participants who have been previously treated with anti-PD-(L)1 therapy. Part 1: Cohort 1 retifanlimab INCAGN01876 every 2 weeks (Q2W) with retifanlimab every 4 weeks (Q4W). Part 1: Cohort 1 INCAGN01876 INCAGN01876 every 2 weeks (Q2W) with retifanlimab every 4 weeks (Q4W). Part 2 (Expansion): Treatment Group B INCAGN01876 INCAGN01876 and retifanlimab combination in participants who are naive to anti-PD-(L)1 therapy. Part 2 (Expansion): Treatment Group A INCAGN01876 INCAGN01876 and retifanlimab combination in participants who have been previously treated with anti-PD-(L)1 therapy.
- Primary Outcome Measures
Name Time Method Part 1: Participants With Treatment-Emergent Adverse Events (TEAEs) Screening through 90 days after end of treatment, up to 24 months A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Assessed every 8 weeks for 12 months, thereafter every 12 weeks up to the end of treatment, up to 24 months. Defined as the percentage of participants having complete response (CR) or partial response (PR).
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) based on RECIST v1.1 and mRECIST Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
Part 2: Participants With Treatment-Emergent Adverse Events (TEAEs) Screening through 90 days after end of treatment, up to 24 months A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Duration of response (DOR) based on RECIST v1.1 and mRECIST Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
Disease control rate (DCR) based on RECIST v1.1 and mRECIST Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. Defined as the percentage of participants having CR, PR, or stable disease (SD).
Trial Locations
- Locations (17)
University of Maryland-Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
John Theurer Cancer Center, Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Uab Medicine-the Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of California San Diego Medical Center, Moores Cancer Center
🇺🇸La Jolla, California, United States
Toi Clinical Research
🇺🇸Whittier, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Mount Sinai Prime
🇺🇸New York, New York, United States
The Adult Outpatient Pavilion At Vcu
🇺🇸Richmond, Virginia, United States
Providence Portland Med. Ctr
🇺🇸Portland, Oregon, United States
University of Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States