Clinical Trials /

Itacitinib Combined With INCB024360 and/or Itacitinib Combined With INCB050465 in Advanced Solid Tumors

NCT02559492

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Endometrial Adenocarcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Solid Tumors

Interventions

DrugSynonymsArms
ItacitinibINCB039110Group A: Itacitinib + epacadostat
EpacadostatGroup A: Itacitinib + epacadostat
ItacitinibINCB039110Group B: Itacitinib + INCB050465
INCB050465Group 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

NameTypeDescriptionInterventions
Group A: Itacitinib + epacadostatExperimentalGroup A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days.
  • Itacitinib
  • Epacadostat
Group B: Itacitinib + INCB050465ExperimentalGroup B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days.
  • Itacitinib
  • INCB050465

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:Recruiting
Lead Sponsor:Incyte Corporation

Last Updated