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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03522142
• Other study ID #: INCB 81776-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 27, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: December 31, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

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.
• INCMGA00012
INCMGA0012 administered intravenously according to the label as 500 mg every 4 weeks

Locations

Country	Name	City	State
Denmark	Rigshospitalet Uni of Hospital of Copenhagen	Copenhagen
Denmark	Odense University Hospital	Odense C
Netherlands	Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus Medical Center	Rotterdam
Norway	Haukeland University Hospital	Bergen
Norway	Utprøvingsenheten, Oslo University Hospital Radiumhospitalet	Oslo
Sweden	Skane University Hospital Lund	Lund
Sweden	Karolinska University Hospital Solna	Stockholm
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Md Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Denmark,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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
Primary	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
Primary	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	Part 1 and Part 2: Cmax of INCB081776	Maximum observed plasma concentration.	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2: Tmax of INCB081776	Time to maximum plasma concentration.	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2: t½ of INCB081776	Apparent plasma terminal phase disposition half-life	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation	To evaluate the correlation pharmacokinetic and pharmacodynamics of INCB081176	Up to approximately 3 weeks.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Part 1 and Part 2: Cmin of INCB081776	Trough concentration of INCB081776	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2: AUC0-8 of INCB081776	Area under the single-dose plasma concentration-time curve from Hour 0 to infinity	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2 : CL/F of INCB081776	Oral dose clearance	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2 : ?z of INCB081776	Terminal elimination rate constant	Up to approximately 3 weeks.
Secondary	Part 1 and Part 2 : Vz/F of INCB081776	Apparent oral dose volume of distribution	Up to approximately 3 weeks.