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

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).

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.