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

Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT02646748
Collaborator
(none)
159
17
2
57.9
9.4
0.2

Study Details

Study Description

Brief Summary

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).

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) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

Study Design

Study Type:
Interventional
Actual Enrollment :
159 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors
Actual Study Start Date :
Jan 25, 2016
Actual Primary Completion Date :
Nov 7, 2019
Actual Study Completion Date :
Nov 20, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: pembrolizumab + itacitinib

Part 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.

Drug: Pembrolizumab
Pembrolizumab 200 mg IV Q3W.

Drug: itacitinib
Itacitinib tablets administered orally once daily.
Other Names:
  • INCB039110
  • Experimental: pembrolizumab + INCB050465

    Part 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, non-small lung cancer and urothelial cancer.

    Drug: Pembrolizumab
    Pembrolizumab 200 mg IV Q3W.

    Drug: INCB050465
    INCB050465 tablets administered orally once daily.

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Evaluation of safety and tolerability as measured by the frequency, duration, and severity of adverse events [Duration of study treatment and up to 120 days after the last dose of study drug]

    Secondary Outcome Measures

    1. Part 1 and 2: Objective Response Rate (ORR) as determined by radiographic disease assessments per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1 criteria [Every 9 weeks for the first year on study]

    2. Part 1 and 2: Change in the number of Tumor Infiltrating Lymphocytes(TILs) and the ratio of CD8+ lymphocytes to FOXP3+ cells infiltrating tumor post-treatment versus pretreatment by IHC [Up to 5 weeks on study treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female, age 18 years or older.

    • Willingness to provide written informed consent for the study.

    • Has a core or excisional baseline tumor biopsy specimen available or willingness to undergo a pre study treatment tumor biopsy to obtain the specimen.

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

    • Presence of measureable disease based on RECIST v1.1

    • 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

    For subjects with SCLC:

    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.

    For subjects with NSCLC:

    Subjects with a histologically or cytologically confirmed diagnosis of Stage IIIB, Stage IV, or recurrent NSCLC. Have not received more than 1 prior systemic therapy for metastatic NSCLC. No prior therapy with checkpoint inhibitors (anti-PD-1/PD-L1 or anti-CTLA-4). Have confirmation that EGFR or ALK-directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations AND ALK gene rearrangements treatable with a tyrosine kinase inhibitor (TKI) OR presence of a KRAS mutation). If participant's tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK translocation will not be required as this is not part of current diagnostic guidelines. Have measurable disease based on RECIST 1.1.

    For subjects with UC:

    Subjects with a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Have had 1 prior treatment of systemic chemotherapy containing a platinum agent or is considered ineligible to receive cisplatin-based combination therapy. No prior therapy with checkpoint inhibitors (anti-PD-1/PD-L1 or anti-CTLA-4). Have measurable disease based on RECIST 1.1.

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco California United States 94143
    2 John Wayne Cancer Institute at Providence Saint John's Health Center Santa Monica California United States 90404
    3 Georgetown University Medical Center Lombardi CCC Washington District of Columbia United States 20007
    4 Hematology-Oncology Associates of Treasure Coast Port Saint Lucie Florida United States 37952
    5 Emory University, Winship Cancer Institute Atlanta Georgia United States 30322
    6 University of Kentucky, Markey Cancer Center Lexington Kentucky United States 40536
    7 The Center for Cancer and Blood Disorders (RCCA MD LLC-Maryland Vidision) Bethesda Maryland United States 20817
    8 Beth Israel Medical Deaconess Medical Center Boston Massachusetts United States 02215
    9 Dana Farber Cancer institute Boston Massachusetts United States 02215
    10 Karmanos Cancer Center Detroit Michigan United States 48201
    11 Henry Ford Hospital System Detroit Michigan United States 48202
    12 St. Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    13 NYU Laura & Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    14 Duke Cancer Institute Durham North Carolina United States 27710
    15 UPMC CancerCenters, Hilman Cancer Center Pittsburgh Pennsylvania United States 15232
    16 HOPE Cancer Center of East Texas Tyler Texas United States 75701
    17 Utah Cancer Specialists Salt Lake City Utah United States 84106

    Sponsors and Collaborators

    • Incyte Corporation

    Investigators

    • Study Director: Peter B. Langmuir, MD, Incyte Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT02646748
    Other Study ID Numbers:
    • 39110-107
    First Posted:
    Jan 6, 2016
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Incyte Corporation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 31, 2022