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

Official Title: A Phase 1B/2 Study of the Safety and Tolerability of Itacitinib (INCB039110) in Combination With Gemcitabine and Nab-Paclitaxel in Subjects With Advanced Solid Tumors

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

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.

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