An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies

Incyte

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Solid Tumors and Hematologic Malignancy

Treatments: Drug: nivolumab; Drug: INCB059872; Drug: all-trans retinoic acid (ATRA); Drug: azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02712905

2017-001710-28 (EudraCT Number)

INCB 59872-101

Details and patient eligibility

About

This is an open-label, dose-escalation/dose-expansion study of INCB059872 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (mono therapy dose escalation) will determine the recommended dose(s) of INCB059872 for dose expansion, based on maximum tolerated dose and/or a tolerated pharmacologically active dose. Part 2 (dose expansion) will further determine the safety, tolerability, efficacy, PK, and PD of the selected monotherapy dose(s) in AML/MDS, SCLC, myelofibrosis, Ewing sarcoma, and poorly differentiated neuroendocrine tumors. Part 3 will determine the recommended dose(s) of INCB059872 in combination with azacitadine and all-trans retinoic acid in AML and in combination with nivolumab in SCLC. Part 4 will further determine the safety, tolerability, efficacy, PK, and PD of the selected combination dose(s) in Part 3.

Enrollment: 116 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female subjects, age 18 years or older.
• Presence of measurable disease that has been confirmed by histology or cytology.
• Must not be a candidate for potentially curative therapy or standard-of-care approved therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Exclusion criteria

• Receipt of anticancer medications, anticancer therapies, or investigational drugs within the defined interval before the first administration of study drug.
• Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve.
• Laboratory and medical history parameters outside Protocol-defined range.
• Known additional malignancy that is progressing or requires active treatment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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116 participants in 2 patient groups

INCB059872

Experimental group

Treatment:

Drug: INCB059872

INCB059872 in combination with other therapies

Experimental group

Description:

Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups: * Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML. * Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML * Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment. Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).

Treatment:

Drug: azacitidine

Drug: all-trans retinoic acid (ATRA)

Drug: INCB059872

Drug: nivolumab