INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Phase 2, Open-Label, Multicenter Study of INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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).

Study Overview

• Status: Withdrawn
• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma; Advanced Malignancies; Metastatic Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Biological: INCAGN01876; Biological: retifanlimab

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)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Uab Medicine-the Kirklin Clinic
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Medical Center, Moores Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Whittier, California, United States, 90603
      • TOI Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland-Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center, Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Prime
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Med. Ctr
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23219
      • The Adult Outpatient Pavilion At Vcu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Cohort 1; INCAGN01876 every 2 weeks (Q2W) with retifanlimab every 4 weeks (Q4W).	Biological: INCAGN01876; INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.; Biological: retifanlimab; retifanlimab will be administered via IV Q4W
Experimental: Part 1: Cohort 2; INCAGN01876 Q2W with retifanlimab Q4W.	Biological: INCAGN01876; INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.; Biological: retifanlimab; retifanlimab will be administered via IV Q4W
Experimental: Part 2 (Expansion): Treatment Group A; INCAGN01876 and retifanlimab combination in participants who have been previously treated with anti-PD-(L)1 therapy.	Biological: INCAGN01876; INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.; Biological: retifanlimab; retifanlimab will be administered via IV Q4W
Experimental: Part 2 (Expansion): Treatment Group B; INCAGN01876 and retifanlimab combination in participants who are naive to anti-PD-(L)1 therapy.	Biological: INCAGN01876; INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.; Biological: retifanlimab; retifanlimab will be administered via IV Q4W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	Screening through 90 days after end of treatment, up to 24 months
Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Defined as the percentage of participants having complete response (CR) or partial response (PR).	Assessed every 8 weeks for 12 months, thereafter every 12 weeks up to the end of treatment, up to 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR) based on RECIST v1.1 and mRECIST	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.	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months.
Disease control rate (DCR) based on RECIST v1.1 and mRECIST	Defined as the percentage of participants having CR, PR, or stable disease (SD).	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months.
Progression-free survival (PFS) based on RECIST v1.1 and mRECIST	Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months.
Part 2: Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	Screening through 90 days after end of treatment, up to 24 months

Collaborators and Investigators

• Sponsor: Incyte Biosciences International Sàrl
• Investigators: Study Director: Nawel Bourayou, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2023
• Primary Completion (Estimated): April 20, 2024
• Study Completion (Estimated): January 11, 2025

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: May 3, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: carcinoma; HNSCC; SCCHN; squamous cell carcinoma of head and neck; carcinoma, squamous cell; anti-PD-(L)1 therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: INCAGN 1876-204

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