Business decision; no safety concerns

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).

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)

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

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

Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.

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.

open-label study