A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors

Incyte Corporation149 enrolled

Overview

The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

149

Conditions

Biliary Tract Cancer (BTC)Colorectal Cancer (CRC)Endometrial Cancer Gastroesophageal Cancer (GC)Ovarian Cancer Solid Tumors

Interventions

INCB001158DRUG

Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.

OxaliplatinDRUG

Oxaliplatin administered intravenously at the protocol-defined dose and schedule.

LeucovorinDRUG

Leucovorin at the protocol-defined dose and regimen.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors. * Presence of measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. * Resolution of treatment-related toxicities. * Adequate hepatic, renal, cardiac, and hematologic function. * Additional cohort-specific criteria may apply. Exclusion Criteria: * Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose. * Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug. * Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment. * Has received prior approved radiotherapy within 14 days of study therapy. * Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Has an active infection requiring systemic therapy. * Has known active CNS metastases and/or carcinomatous meningitis. * Women who are pregnant or breastfeeding.

Locations (10)

University of Alabama

Birmingham, Alabama, United States

USA Mitchell Cancer Center

Mobile, Alabama, United States

UC Davis - Comprehensive Cancer Centre

Sacramento, California, United States

Outcomes

Primary Outcomes

Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

Time frame: up to 1385 days

Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)

A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.

Time frame: up to Day 28

Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen

The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.

Time frame: up to Day 580

Phase 2: Objective Response Rate (ORR)

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Phase 1: ORR

ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, as determined by investigator assessment of radiographic disease as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the Baseline sum diameters, no new lesions, and no progression of non-target lesions.

Time frame: up to 580 days

Phases 1 and 2: Duration of Response

DOR was defined as the time from initial objective response (CR or PR) (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if it occurred sooner than disease progression. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

Time frame: up to 368 days

Phases 1 and 2: Disease Control Rate

DCR was defined as the percentage of participants with an overall response of CR, PR, or stable disease (SD), as determined by investigator assessment of radiographic disease as per RECIST v1.1, for at least 8 weeks. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Time frame: up to 1385 days

Phases 1 and 2: Progression-free Survival

According to RECIST 1.1, PFS was defined as the length of time from the date of the first dose study of drug until the earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death due to any cause, if it occurred sooner than progression.

Time frame: up to 1385 days

Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration

Cmin was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

Time frame: Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection

Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration

Cmax was defined as the maximum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

Time frame: Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration

tmax was defined as the time to the maximum concentration. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration

AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration

tlast was defined as the time of the last sample collected from which a concentration was measured. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.