Safety Study of Itacitinib (INCB039110) in Combination With Gemcitabine and Nab-Paclitaxel in Subjects With Advanced Solid Tumors

Phase 1

Completed

Interventions: Drug: itacitinib
Drug: Gemcitabine
Drug: nab-paclitaxel
Drug: filgrastim

Brief Summary: Test the hypothesis that itacitinib (INCB039110) can be administered safely in combination with gemcitabine and nab-paclitaxel in subjects with advanced or metastatic cancer.

Detailed Description: Study Part 1: This is a dose optimization phase designed to find a tolerated regimen that includes identifying the MTD of itacitinib (INCB039110) (within a defined pharmacologic range) in combination with doses of gemcitabine and nab-paclitaxel that have established safety and tolerability in subjects with advanced or metastatic solid tumors.

Study Part 2 and Part 2A: This phase will explore the safety and tolerability of the MTD or PAD of itacitinib (INCB039110) when administered in combination with gemcitabine and nab-paclitaxel in subjects with untreated advanced or metastatic pancreatic cancer.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed solid tumor (Part 1) or pancreatic adenocarcinoma (Part 2)
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Received no more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neo-adjuvant and/or adjuvant therapy) (Part 1)
Received no prior chemotherapy for advanced or metastatic disease (Part 2 and Part 2a)
Adequate renal, hepatic, and bone marrow function without frequent blood product or hematopoietic growth factor support (eg use of erythropoietin or transfusions > 2 units packed red blood cells every 3 months)
Ability to swallow and retain oral medication

Exclusion Criteria

Any known contraindications to the use of a required comedication (gemcitabine or nab-paclitaxel).
Evidence of uncontrolled brain metastases or history of uncontrolled seizures.
Ongoing radiation therapy and/or radiation therapy administered within 28 days of enrollment or ongoing radiotherapy-related toxicities.
Presence of ≥ Grade 2 neuropathy.
Inability to swallow food or any condition of the upper GI tract that precludes administration of oral medications.
Recent (≤ 3 months) history of partial or complete bowel obstruction.
Unwillingness to be transfused with blood components.
Known history of Hepatitis B or C infection or HIV infection

Arm && Interventions

Group	Intervention	Description
itacitinib, gemcitabine, nab-paclitaxel, filgrastim	itacitinib	-
itacitinib, gemcitabine, nab-paclitaxel, filgrastim	Gemcitabine	-
itacitinib, gemcitabine, nab-paclitaxel, filgrastim	nab-paclitaxel	-
itacitinib, gemcitabine, nab-paclitaxel, filgrastim	filgrastim	-

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of combination therapy study treatment itacitinib (INCB039110) plus nab-paclitaxel and gemcitabine as measured by the number of participants with adverse events	Baseline and weekly for Cycle 1 and then Day 1, Week 8 and Week 15 for all subsequent cycles until the End of Treatment visit (approximately 6 months).
Identify the Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD) within a defined dose range for itacitinib (INCB039110) in the treatment regimens administered	Each cohort will be observed for a minimum of 28 days.

Secondary Outcome Measures

Name	Time	Method
Clinical activity as measured by the greatest decrease in tumor burden compared to baseline.	Baseline and approximately every two cycles throughout the study until study completion or early termination (approximately 6 months).
Pharmacokinetics of gemcitabine and paclitaxel administered with or without concurrent itacitinib (INCB039110)	Baseline up to 6 months.