Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors
A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors
1 other identifier
interventional
159
1 country
17
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2016
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 4, 2016
CompletedFirst Posted
Study publicly available on registry
January 6, 2016
CompletedStudy Start
First participant enrolled
January 25, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 7, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 20, 2020
CompletedMarch 31, 2022
March 1, 2022
3.8 years
January 4, 2016
March 30, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (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 Outcomes (2)
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
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
Study Arms (2)
pembrolizumab + itacitinib
EXPERIMENTALPart 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 + INCB050465
EXPERIMENTALPart 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.
Interventions
Itacitinib tablets administered orally once daily.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
University of California San Francisco Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143, United States
John Wayne Cancer Institute at Providence Saint John's Health Center
Santa Monica, California, 90404, United States
Georgetown University Medical Center Lombardi CCC
Washington D.C., District of Columbia, 20007, United States
Hematology-Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, 37952, United States
Emory University, Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Kentucky, Markey Cancer Center
Lexington, Kentucky, 40536, United States
The Center for Cancer and Blood Disorders (RCCA MD LLC-Maryland Vidision)
Bethesda, Maryland, 20817, United States
Beth Israel Medical Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer institute
Boston, Massachusetts, 02215, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
Henry Ford Hospital System
Detroit, Michigan, 48202, United States
St. Luke's Hospital of Kansas City
Kansas City, Missouri, 64111, United States
NYU Laura & Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
UPMC CancerCenters, Hilman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
HOPE Cancer Center of East Texas
Tyler, Texas, 75701, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Related Publications (1)
Munster P, Iannotti N, Cho DC, Kirkwood JM, Villaruz LC, Gibney GT, Hodi FS, Mettu NB, Jones M, Bowman J, Smith M, Lakshminarayanan M, O'Day S. Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study. Cancer Res Commun. 2023 Dec 19;3(12):2572-2584. doi: 10.1158/2767-9764.CRC-22-0461.
PMID: 38115208DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Peter B. Langmuir, MD
Incyte Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 4, 2016
First Posted
January 6, 2016
Study Start
January 25, 2016
Primary Completion
November 7, 2019
Study Completion
November 20, 2020
Last Updated
March 31, 2022
Record last verified: 2022-03