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

Incyte

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: INCB081776; Drug: INCMGA00012

Study type: Interventional

Funder types: Industry

Identifiers

NCT03522142

2020-004867-26 (EudraCT Number)

2023-504499-29-00 (Registry Identifier)

INCB 81776-101

Details and patient eligibility

About

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).

Enrollment: 83 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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83 participants in 2 patient groups

INCB081776

Experimental group

Description:

Single-agent INCB081776.

Treatment:

Drug: INCB081776

INCB081776 + INCMGA00012

Experimental group

Description:

INCB081776 in combination with INCMGA00012.

Treatment:

Drug: INCMGA00012

Drug: INCB081776