Clinical Trials/NCT03522142

NCT03522142

Terminated

Phase 1

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

Incyte Corporation18 sites in 5 countries83 target enrollmentAugust 27, 2018

ConditionsAdvanced Solid Tumors

InterventionsINCB081776 INCMGA00012

DrugsINCB081776 INCMGA00012

Overview

Phase: Phase 1
Intervention: INCB081776
Conditions: Advanced Solid Tumors
Sponsor: Incyte Corporation
Enrollment: 83
Locations: 18
Primary Endpoint: Part 2 (2A & B): RDE in combination with INCMGA00012
Status: Terminated
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

August 27, 2018

End Date

September 10, 2025

Last Updated

6 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Incyte Corporation

Responsible Party

Sponsor

Eligibility Criteria

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.
•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.
•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
•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.

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.

Arms & Interventions

INCB081776

Single-agent INCB081776.

Intervention: INCB081776

INCB081776 + INCMGA00012

INCB081776 in combination with INCMGA00012.

Intervention: INCB081776

INCB081776 + INCMGA00012

INCB081776 in combination with INCMGA00012.

Intervention: INCMGA00012

Outcomes

Primary Outcomes

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

Time Frame: Up to one year

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

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

Time Frame: Up to one year

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

Part 2 (2A & 2B): Number of treatment-emergent adverse events

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

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.

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.

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.

Secondary Outcomes

Part 1 and Part 2: Cmax of INCB081776(Up to approximately 3 weeks.)
Part 1 and Part 2: Disease control rate(Up to approximately 1 year.)
Part 1 and Part 2: Cmin 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: Duration of response(Up to approximately 1 year.)
Part 1 and Part 2 : λz 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: AUC0-t 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: Overall response rate(Up to approximately 1 year.)
Part 1 and Part 2: AUC0-∞ of INCB081776(Up to approximately 3 weeks.)
Part 1 and Part 2 : CL/F of INCB081776(Up to approximately 3 weeks.)
Part 1 and Part 2 : Vz/F of INCB081776(Up to approximately 3 weeks.)