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

March 30, 2022 updated by: Incyte Corporation

A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

159

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1: 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
Duration of study treatment and up to 120 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Every 9 weeks for the first year on study
Every 9 weeks for the first year on study
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
Time Frame: Up to 5 weeks on study treatment
Up to 5 weeks on study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2016

Primary Completion (Actual)

November 7, 2019

Study Completion (Actual)

November 20, 2020

Study Registration Dates

First Submitted

January 4, 2016

First Submitted That Met QC Criteria

January 4, 2016

First Posted (Estimate)

January 6, 2016

Study Record Updates

Last Update Posted (Actual)

March 31, 2022

Last Update Submitted That Met QC Criteria

March 30, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 39110-107

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Pembrolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cameroon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe