A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies

A Phase 1a/1b Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent INCB081776 (Part 1) and INCB081776 in combination with INCMGA00012 (Part 2).

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: INCB081776; Drug: INCMGA00012

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 02100
    • Rigshospitalet Uni of Hospital of Copenhagen
  • Odense C, Denmark, 05000
    • Odense University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medical Center
• Norway
  • Bergen, Norway, 05021
    • Haukeland University Hospital
  • Oslo, Norway, 00379
    • Utprøvingsenheten, Oslo University Hospital Radiumhospitalet
• Sweden
  • Lund, Sweden, 22185
    • Skane University Hospital Lund
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital Solna
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female participants at least 18 years of age with advanced malignancies who have received or been intolerant to standard therapy:

Parts 1A and 2A:

• Histologically confirmed advanced or metastatic gastric or GEJ adenocarcinoma, HCC, melanoma, NSCLC, RCC, soft-tissue sarcoma, SCCHN (recurrent or metastatic), TNBC, or urothelial carcinoma. Additional tumor histologies, including MSI-H tumors, may be allowed with approval from the medical monitor.
• Measurable disease per RECIST v1.1.

Parts 1B and 2B:

• Histologic confirmation of the cohort-specific tumor types specified below: Cohort 1 - Advanced or metastatic melanoma Cohort 2 - Advanced or metastatic NSCLC Cohort 3 - Recurrent or metastatic SCCHN Cohort 4 - Advanced or metastatic soft-tissue sarcoma

• Cohorts 1-3 must have received 1 prior PD-1/L1 treatment and have experienced PD during or after that treatment and have progressed on other SOC therapy(ies); Cohort 4 must be PD-1/L1 treatment naïve but have progressed on SOC therapy(ies).
• Measurable disease per RECIST v1.1.
• Must be willing to submit to a fresh baseline tumor biopsy and an on-treatment biopsy between Cycle 2 Day 1 and Cycle 3 Day 1.
• Care should be taken to biopsy the same lesion for the baseline and on-treatment samples. If a participant has a solitary target lesion, this should not be biopsied.

Part 1C:

• Participants with relapsed/refractory AML following standard therapy; acute promyelocytic leukemia (M3) and therapy-related AML are excluded.
• FLT3-ITD and IDH1/2 wild-type or mutated are eligible; appropriate targeted therapy for participants with actionable mutations must have been received.

Exclusion Criteria:

• Laboratory values not within the protocol-defined range.
• History of retinal disease as defined in the protocol.
• Clinically significant cardiac disease as per protocol-defined criteria.
• History or presence of an ECG that, in the investigator's opinion, is clinically meaningful as per protocol-defined criteria.
• Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.
• Active or inactive autoimmune disease or syndrome that has required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease.
• Prior Grade 3 or higher immune-related AEs or any ocular toxicity on prior immunotherapy as per protocol-defined criteria.
• Receipt of any vitamin K antagonists, systemic corticosteroids, live vaccines, or treatment with any anticancer medications or investigational drugs within the protocol-defined intervals.
• Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
• Active infection requiring systemic therapy.
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
• Known history of HIV (HIV 1/2 antibodies).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INCB081776; Single-agent INCB081776.	Drug: INCB081776; INCB081776 administered once or twice daily orally with water after a fast of at least 2 hours before and at least 1 hour after the dose.
Experimental: INCB081776 + INCMGA00012; INCB081776 in combination with INCMGA00012.	Drug: INCB081776; INCB081776 administered once or twice daily orally with water after a fast of at least 2 hours before and at least 1 hour after the dose.; Drug: INCMGA00012; INCMGA0012 administered intravenously according to the label as 500 mg every 4 weeks; Other Names: retifanlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (1A and 1B): Number of 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 first dose of study drug.	Screening through 90 days after end of treatment, up to approximately 1 year.
Part 1 (1A and 1B): Recommended Dose for Expansion (RDE)	Recommended dose as a monotherapy as measured by safety, PK and data	Up to one year
Part 2 (2A & 2B): Number of treatment-emergent adverse events	A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.	Screening through 90 days after end of treatment, up to approximately 1 year
Part 2 (2A & B): RDE in combination with INCMGA00012	Recommended dose as a combination as measured by safety, PK and data	Up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Cmax of INCB081776	Maximum observed plasma concentration.	Up to approximately 3 weeks.
Part 1 and Part 2: Tmax of INCB081776	Time to maximum plasma concentration.	Up to approximately 3 weeks.
Part 1 and Part 2: t½ of INCB081776	Apparent plasma terminal phase disposition half-life	Up to approximately 3 weeks.
Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation	To evaluate the correlation pharmacokinetic and pharmacodynamics of INCB081176	Up to approximately 3 weeks.
Part 1 and Part 2: Overall response rate	Defined as the percentage of participants having complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to approximately 1 year.
Part 1 and Part 2: Disease control rate	Defined as the percentage of participants having CR, PR, or stable disease (SD) per RECIST v1.1.	Up to approximately 1 year.
Part 1 and Part 2: Duration of response	Defined as the time from earliest date of disease response until the earliest date of disease progression (per RECIST v1.1) or death due to any cause, if occurring sooner than progression.	Up to approximately 1 year.
Part 1 and Part 2: AUC0-t of INCB081776	Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration	Up to approximately 3 weeks.
Part 1 and Part 2: Cmin of INCB081776	Trough concentration of INCB081776	Up to approximately 3 weeks.
Part 1 and Part 2: AUC0-∞ of INCB081776	Area under the single-dose plasma concentration-time curve from Hour 0 to infinity	Up to approximately 3 weeks.
Part 1 and Part 2 : CL/F of INCB081776	Oral dose clearance	Up to approximately 3 weeks.
Part 1 and Part 2 : λz of INCB081776	Terminal elimination rate constant	Up to approximately 3 weeks.
Part 1 and Part 2 : Vz/F of INCB081776	Apparent oral dose volume of distribution	Up to approximately 3 weeks.

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Diane Hershock, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2018
• Primary Completion (Actual): September 10, 2025
• Study Completion (Actual): September 10, 2025

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: April 30, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: PD-1; Advanced solid tumors; AXL; AXL/MER; MER
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: INCB 81776-101; 2020-004867-26 (EudraCT Number); 2023-504499-29-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No