Clinical Trials /

Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

NCT02646748

Description:

This is an open-label, multicenter, Phase 1b platform study in subjects with advanced or metastatic solid tumors (Part 1a) and subjects with selected solid tumors (Part 1b and Part 2). Two treatment groups (Group A and Group B) will be evaluated Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination. Once the recommended dose has been identified in Part 1a, subjects with select solid tumor types will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination. Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors
  • Official Title: A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 39110-107
  • NCT ID: NCT02646748

Conditions

  • Advanced Solid Tumors
  • Endometrial Cancer
  • Melanoma
  • Microsatellite Unstable (MSI) Colorectal Cancer
  • MMR-deficient Tumors
  • Non-small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Triple Negative Breast Cancer
  • Transitional Cell Carcinoma of the Genitourinary Tract
  • Pancreatic Ductal Adenocarcinoma
  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Pembrolizumabpembrolizumab + itacitinib
itacitinibINCB039110pembrolizumab + itacitinib
INCB050465pembrolizumab + INCB050465

Purpose

This is an open-label, Phase 1b, 3 Part (Part 1a, Part 1b and Part 2), multi-center study. Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination. Once the recommended dose has been identified in Part 1a, subjects with select solid tumor types will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination. Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC).

Detailed Description

      This is an open-label, Phase 1b, 3 Part (Part 1a, Part 1b, and Part 2), multi-center study.

      Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced
      solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib
      (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a
      PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum
      tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each
      combination.

      Once the recommended dose has been identified in Part 1a, subjects with endometrial cancer,
      gastric cancer, melanoma, microsatellite unstable (MSI) colorectal cancer or other
      MMR-deficient tumors, non-small cell lung cancer, renal cell carcinoma, head and neck
      squamous cell carcinoma, triple negative breast cancer, pancreatic ductal carcinoma, or
      transitional cell carcinoma of the genitourinary tract will be enrolled into safety
      expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent
      (Part 1b) for each combination.

      Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with
      pembrolizumab in patients with small cell lung cancer (SCLC).
    

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab + itacitinibExperimentalPart 1a Group A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group A-1 and Group A-2 will evaluate the MTD or PAD of itacitinib in combination with pembrolizumab in subjects with select solid tumors.
  • Pembrolizumab
  • itacitinib
pembrolizumab + INCB050465ExperimentalPart 1a Group B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group B-1 and Group B-2 will evaluate the MTD or PAD of INCB050465 in combination with pembrolizumab in subjects with select solid tumors. Part 2 will evaluate the combination of INCB050465 in combination with pembrolizumab in subjects with small cell lung cancer
  • Pembrolizumab
  • INCB050465

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female, age 18 years or older.

          -  Willingness to provide written informed consent for the study.

          -  Has baseline tumor biopsy specimen available or willingness to undergo a pretreatment
             tumor biopsy to obtain the specimen.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  For Part 1a: Subjects with histologically or cytologically confirmed advanced or
             metastatic solid tumors that have failed prior standard therapy (including subject
             refusal or intolerance).

          -  For Part 1b: Subjects with histologically or cytologically confirmed advanced or
             metastatic endometrial cancer, gastric cancer, melanoma, microsatellite unstable
             (MSI) colorectal cancer or other MMR-deficient tumors, non-small cell lung cancer,
             renal cell carcinoma, head and neck squamous cell carcinoma, triple negative breast
             cancer, pancreatic ductal carcinoma, or 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, been
             intolerant to treatment, or refused standard treatment.

          -  For Part 1b: Must have documented confirmed disease progression on a prior PD-1
             pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.

          -  For Part 2: Subjects with histologically or cytologically confirmed advanced or
             metastatic SCLC. Must not have had previous treatment with antibodies that modulate
             T-cell function or checkpoint pathways. Must have disease progression on or after
             platinum-based chemotherapy or must be intolerant to or refuse standard treatment.
             Must not have received more than 2 lines of prior therapy.

        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:Evaluation of safety and tolerability as measured by the frequency, duration, and severity of adverse events
Time Frame:Duration of study treatment and up to 120 days after the last dose of study drug
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) as determined by radiographic disease assessments per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1 criteria
Time Frame:Every 9 weeks for the first year on study
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) as measured by the duration from the date of first dose until the earliest date of disease progression or death as measured by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1
Time Frame:Every 9 weeks for the first year on study
Safety Issue:
Description:
Measure:Duration of response (DOR) as measured from the time of the earliest response complete response (CR) or partial response (PR) until disease progression per irRECIST v1.1
Time Frame:Every 9 weeks for the first year on study
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Advanced

Last Updated

February 2, 2017