Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors
Colon/Rectal Cancer
Lung Cancer
Melanoma
Stomach/ Gastric Cancer
18 Years and older, Male and Female
39110-107 (primary)
NCI-2016-00648
s15-00941
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).
Objectives
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).
Eligibility
- 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.
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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