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

NCT ID: NCT03522142

Last Updated: 2025-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-27

Study Completion Date

2025-09-10

Brief Summary

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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).

Detailed Description

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Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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INCB081776

Single-agent INCB081776.

Group Type EXPERIMENTAL

INCB081776

Intervention Type DRUG

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.

INCB081776 + INCMGA00012

INCB081776 in combination with INCMGA00012.

Group Type EXPERIMENTAL

INCB081776

Intervention Type DRUG

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.

INCMGA00012

Intervention Type DRUG

INCMGA0012 administered intravenously according to the label as 500 mg every 4 weeks

Interventions

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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.

Intervention Type DRUG

INCMGA00012

INCMGA0012 administered intravenously according to the label as 500 mg every 4 weeks

Intervention Type DRUG

Other Intervention Names

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retifanlimab

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Diane Hershock, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Md Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Rigshospitalet Uni of Hospital of Copenhagen

Copenhagen, , Denmark

Site Status

Odense University Hospital

Odense C, , Denmark

Site Status

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Haukeland University Hospital

Bergen, , Norway

Site Status

Utprøvingsenheten, Oslo University Hospital Radiumhospitalet

Oslo, , Norway

Site Status

Skane University Hospital Lund

Lund, , Sweden

Site Status

Karolinska University Hospital Solna

Stockholm, , Sweden

Site Status

Countries

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United States Denmark Netherlands Norway Sweden

Other Identifiers

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2023-504499-29-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-004867-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 81776-101

Identifier Type: -

Identifier Source: org_study_id

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