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Advanced Solid TumorsPhase 1NCT03522142

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

A Phase 1 study testing INCB081776 and INCMGA00012 in people with Advanced Solid Tumors, run by Incyte Corporation at 18 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
INCB081776 and INCMGA00012
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
18 sitesin 5 countries
Study dates
27 Aug 2018to 10 Sep 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

18 sites in 5 countries.

18 sites in 5 countries

United States9 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Md Anderson Cancer Center

    Houston, Texas, 77030

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Yale Cancer Center

    New Haven, Connecticut, 06510

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

Netherlands3 sites

  • Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • University Medical Center Groningen

    Groningen, 9713GZ

  • Erasmus Medical Center

    Rotterdam, 3015 GD

Other trials in Netherlands

Denmark2 sites

  • Rigshospitalet Uni of Hospital of Copenhagen

    Copenhagen, 02100

  • Odense University Hospital

    Odense C, 05000

Other trials in Denmark

Norway2 sites

  • Haukeland University Hospital

    Bergen, 05021

  • Utprøvingsenheten, Oslo University Hospital Radiumhospitalet

    Oslo, 00379

Other trials in Norway

Sweden2 sites

  • Skane University Hospital Lund

    Lund, 22185

  • Karolinska University Hospital Solna

    Stockholm, 171 76

Other trials in Sweden

About this study

Official title: 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).

Being tested
INCB081776, INCMGA00012
Keywords
Advanced solid tumors, AXL, MER, AXL/MER, PD-1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INCB081776Drug

    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.

  • INCMGA00012Drug

    Also called retifanlimab

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

Study groups in NCT03522142
Study groupRoleWhat they receive
INCB081776ExperimentalSingle-agent INCB081776.
Receives: Drug: INCB081776
INCB081776 + INCMGA00012ExperimentalINCB081776 in combination with INCMGA00012.
Receives: Drug: INCB081776; Drug: INCMGA00012

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Screening through 90 days after end of treatment, up to approximately 1 year.

  2. Part 1 (1A and 1B): Recommended Dose for Expansion (RDE)

    Recommended dose as a monotherapy as measured by safety, PK and data

    Measured: Up to one year

  3. 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.

    Measured: Screening through 90 days after end of treatment, up to approximately 1 year

  4. Part 2 (2A & B): RDE in combination with INCMGA00012

    Recommended dose as a combination as measured by safety, PK and data

    Measured: Up to one year

Secondary outcomes (13)

  1. Part 1 and Part 2: Cmax of INCB081776

    Maximum observed plasma concentration.

    Measured: Up to approximately 3 weeks.

  2. Part 1 and Part 2: Tmax of INCB081776

    Time to maximum plasma concentration.

    Measured: Up to approximately 3 weeks.

  3. Part 1 and Part 2: t½ of INCB081776

    Apparent plasma terminal phase disposition half-life

    Measured: Up to approximately 3 weeks.

  4. Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation

    To evaluate the correlation pharmacokinetic and pharmacodynamics of INCB081176

    Measured: Up to approximately 3 weeks.

  5. 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.

    Measured: Up to approximately 1 year.

  6. 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.

    Measured: Up to approximately 1 year.

  7. 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.

    Measured: Up to approximately 1 year.

  8. 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

    Measured: Up to approximately 3 weeks.

  9. Part 1 and Part 2: Cmin of INCB081776

    Trough concentration of INCB081776

    Measured: Up to approximately 3 weeks.

  10. Part 1 and Part 2: AUC0-∞ of INCB081776

    Area under the single-dose plasma concentration-time curve from Hour 0 to infinity

    Measured: Up to approximately 3 weeks.

  11. Part 1 and Part 2 : CL/F of INCB081776

    Oral dose clearance

    Measured: Up to approximately 3 weeks.

  12. Part 1 and Part 2 : λz of INCB081776

    Terminal elimination rate constant

    Measured: Up to approximately 3 weeks.

  13. Part 1 and Part 2 : Vz/F of INCB081776

    Apparent oral dose volume of distribution

    Measured: Up to approximately 3 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2018
  2. Study start27 Aug 2018
  3. Primary completion10 Sep 2025
  4. Study completion10 Sep 2025

Why it stopped: The study was terminated after careful review of the overall clinical activity of this compound and a lack of robust efficacy. The study closure is not based on safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03522142
Sponsor's protocol ID
INCB 81776-101
Other IDs
2023-504499-29-00, 2020-004867-26, 2023
Status last verified
Oct 2025
First submitted
30 Apr 2018
Last updated
9 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing INCB081776 and INCMGA00012 in people with Advanced Solid Tumors, run by Incyte Corporation at 18 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Netherlands, Denmark, Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated after careful review of the overall clinical activity of this compound and a lack of robust efficacy. The study closure is not based on safety concerns.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 (1A and 1B): Number of treatment-emergent adverse events (TEAEs) (time frame: Screening through 90 days after end of treatment, up to approximately 1 year.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03522142.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.

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