This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Incyte Corporation
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02646748
First received: January 4, 2016
Last updated: August 14, 2017
Last verified: August 2017
  Purpose

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).


Condition Intervention Phase
Advanced Solid Tumors Endometrial Cancer Melanoma Microsatellite Unstable (MSI) Colorectal Cancer MMR-deficient Tumors 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 Drug: Pembrolizumab Drug: itacitinib Drug: INCB050465 Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • 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 ]

Estimated Enrollment: 201
Actual Study Start Date: January 2016
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 and non-small lung cancer.

Drug: Pembrolizumab
Pembrolizumab 200 mg IV Q3W.
Drug: INCB050465
INCB050465 tablets administered orally once daily.

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Subject 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 .

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02646748

Contacts
Contact: Incyte Corporation Call Center 1.855.463.3463

Locations
United States, California
Recruiting
San Francisco, California, United States
Recruiting
Santa Monica, California, United States
United States, District of Columbia
Recruiting
Washington, D.C., District of Columbia, United States
United States, Florida
Recruiting
Port Saint Lucie, Florida, United States
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States
United States, New York
Recruiting
New York, New York, United States
United States, North Carolina
Recruiting
Durham, North Carolina, United States
United States, Pennsylvania
Recruiting
Pittsburgh, Pennsylvania, United States
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Mark Jones, MD Incyte Corporation
  More Information

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02646748     History of Changes
Other Study ID Numbers: 39110-107
Study First Received: January 4, 2016
Last Updated: August 14, 2017

Keywords provided by Incyte Corporation:
Advanced

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Squamous Cell
Colorectal Neoplasms
Adenocarcinoma
Carcinoma, Renal Cell
Small Cell Lung Carcinoma
Endometrial Neoplasms
Triple Negative Breast Neoplasms
Head and Neck Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms

ClinicalTrials.gov processed this record on August 18, 2017