Description:
This is an open-label, Phase 1b, platform study in subjects with advanced or metastatic solid
tumors. The study will be divided into 3 parts (Part 1a, Part 1b, and Part 2). Part 1a will
evaluate a JAK inhibitor with JAK1 selectivity (Itacitinib) in combination with an IDO1
inhibitor (epacadostat; INCB024360; Group A) and Itacitinib in combination with a PI3K-delta
inhibitor (INCB050465; Group B) to determine the MTD or PAD and the recommended Part 1b doses
for each combination. Once the recommended dose has been identified for each treatment group
in Part 1a, subjects with advanced solid tumors will be enrolled into expansion cohorts based
upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b). In Part 2,
additional expansion cohorts will be enrolled to further evaluate lower doses of itacitinib
and INCB050465 in subjects with select tumor types.
Title
- Brief Title: Itacitinib Combined With INCB024360 and/or Itacitinib Combined With INCB050465 in Advanced Solid Tumors
- Official Title: A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of INCB Combinations in Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
39110-106
- NCT ID:
NCT02559492
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Itacitinib | INCB039110 | Group A: Itacitinib + epacadostat |
Epacadostat | | Group A: Itacitinib + epacadostat |
Itacitinib | INCB039110 | Group B: Itacitinib + INCB050465 |
INCB050465 | | Group B: Itacitinib + INCB050465 |
Purpose
This is an open-label, Phase 1b, platform study in subjects with advanced or metastatic solid
tumors. The study will be divided into 3 parts (Part 1a, Part 1b, and Part 2). Part 1a will
evaluate a JAK inhibitor with JAK1 selectivity (Itacitinib) in combination with an IDO1
inhibitor (epacadostat; INCB024360; Group A) and Itacitinib in combination with a PI3K-delta
inhibitor (INCB050465; Group B) to determine the MTD or PAD and the recommended Part 1b doses
for each combination. Once the recommended dose has been identified for each treatment group
in Part 1a, subjects with advanced solid tumors will be enrolled into expansion cohorts based
upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b). In Part 2,
additional expansion cohorts will be enrolled to further evaluate lower doses of itacitinib
and INCB050465 in subjects with select tumor types.
Trial Arms
Name | Type | Description | Interventions |
---|
Group A: Itacitinib + epacadostat | Experimental | Group A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. | |
Group B: Itacitinib + INCB050465 | Experimental | Group B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. | |
Eligibility Criteria
Inclusion Criteria:
- Male or female, age 18 years or older.
- Willingness to provide written informed consent for the study.
- Part 1a: Subjects with histologically or cytologically confirmed advanced or
metastatic solid tumors that have failed prior standard therapy (including subject
refusal or intolerance).
- Part 1b: Subjects with endometrial cancer, gastric cancer, head and neck squamous cell
carcinoma, melanoma, microsatellite unstable colorectal cancer, non-small cell lung
cancer, pancreatic ductal adenocarcinoma, renal cell carcinoma, triple negative breast
cancer, or transitional cell carcinoma of the genitourinary tract that have had
disease progression after available therapies for metastatic disease that are known to
confer clinical benefit, been intolerant to treatment, or refused standard treatment.
- Part 1b: Must have documented confirmed disease progression on a prior programmed cell
death-1 (PD-1) pathway targeted agent or must be PD-1 pathway-targeted treatment
naïve.
- Part 2: Subjects with HNSCC, NSCLC, pancreatic ductal adenocarcinoma, salivary gland
cancer, and transitional cell carcinoma of the genitourinary tract that have had
disease progression after available therapies for advanced or metastatic disease that
are known to confer clinical benefit, have been intolerant to treatment, or have
refused standard treatment.
- Willingness to undergo a pre-treatment and on-treatment tumor biopsy to obtain the
specimen.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria:
- Laboratory parameters not within the protocol-defined range.
- Receipt of anticancer medications or investigational drugs within a defined interval
before the first administration of study drug.
- Received an immune-suppressive based treatment for any reason within 14 days prior to
the first dose of study treatment.
- Has not recovered from toxic effect of prior therapy to < Grade 1.
- Active or inactive autoimmune process.
- Has received a live vaccine within 30 days of planned start of study therapy.
- Active infection requiring systemic therapy.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With Dose Limiting Toxicities (DLTs) |
Time Frame: | Baseline through 21 days |
Safety Issue: | |
Description: | Safety and tolerability of the treatment groups. |
Secondary Outcome Measures
Measure: | Objective response rate (ORR) |
Time Frame: | Every 9 weeks for duration of study participation which is estimated to be 18 months |
Safety Issue: | |
Description: | Tumor response rates in those subjects with measurable disease. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Every 9 weeks for duration of study participation which is estimated to be 18 months |
Safety Issue: | |
Description: | Progression-free survival, defined as the time from enrollment until the earliest date of disease progression. |
Measure: | Duration of response (DOR) |
Time Frame: | Every 9 weeks for duration of study participation which is estimated to be 18 months |
Safety Issue: | |
Description: | Duration of response determined by radiographic disease assessment. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Incyte Corporation |
Last Updated
September 25, 2019