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

NCT03522142 | Terminated Phase 1 FDA Drug

• 3 other identifiers: INCB 81776-1012023-504499-29-002020-004867-26
• Study Type: interventional
• Target: 83
• Locations: 5 countries
• Sites: 18

Brief Summary

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).

Conditions

Advanced Solid Tumors

Keywords

Advanced solid tumors; AXL; MER; AXL/MER; PD-1

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (13)

• Part 1 and Part 2: Cmax of INCB081776

  Up to approximately 3 weeks.

• Part 1 and Part 2: Tmax of INCB081776

  Up to approximately 3 weeks.

• Part 1 and Part 2: t½ of INCB081776

  Up to approximately 3 weeks.

• Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation

  Up to approximately 3 weeks.

• Part 1 and Part 2: Overall response rate

  Up to approximately 1 year.

Study Arms (2)

INCB081776

EXPERIMENTAL

Single-agent INCB081776.

Drug: INCB081776

INCB081776 + INCMGA00012

EXPERIMENTAL

INCB081776 in combination with INCMGA00012.

Drug: INCB081776; Drug: INCMGA00012

Interventions

INCB081776 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; INCB081776 + INCMGA00012

INCMGA00012 DRUG

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

Also known as: retifanlimab

INCB081776 + INCMGA00012

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (18)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Rigshospitalet Uni of Hospital of Copenhagen

Copenhagen, 02100, Denmark

Location

Odense University Hospital

Odense C, 05000, Denmark

Location

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 GD, Netherlands

Location

Haukeland University Hospital

Bergen, 05021, Norway

Location

Utprøvingsenheten, Oslo University Hospital Radiumhospitalet

Oslo, 00379, Norway

Location

Skane University Hospital Lund

Lund, 22185, Sweden

Location

Karolinska University Hospital Solna

Stockholm, 171 76, Sweden

Location

Study Officials

• Diane Hershock, MD

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 11, 2018
• Study Start: August 27, 2018
• Primary Completion: September 10, 2025
• Study Completion: September 10, 2025
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2); SE (2); US (9); NL (3); NO (2)