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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02646748
Other study ID # 39110-107
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date January 25, 2016
Est. completion date November 20, 2020

Study information

Verified date March 2022
Source Incyte Corporation
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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).


Recruitment information / eligibility

Status Completed
Enrollment 159
Est. completion date November 20, 2020
Est. primary completion date November 7, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Secondary 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
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