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).
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
159
Pembrolizumab 200 mg IV Q3W.
Itacitinib tablets administered orally once daily.
INCB050465 tablets administered orally once daily.
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
Georgetown University Medical Center Lombardi CCC
Washington D.C., District of Columbia, United States
Hematology-Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, United States
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States
University of Kentucky, Markey Cancer Center
Lexington, Kentucky, 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
Karmanos Cancer Center
Detroit, Michigan, United States
...and 7 more locations
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
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.