Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma

Inclusion Criteria

• Histologically or cytologically confirmed metastatic PDAC, no more than 1 prior chemotherapy regimen or treatment-naïve patients
• Eastern Cooperative Oncology Group 0 or 1
• At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) scan and that is suitable for accurate repeated measurements
• MEDI4736 + nab-paclitaxel + gemcitabine chemotherapy cohort: treatment-naïve patients with metastatic PDAC who have received no previous systemic chemotherapy 5 MEDI4736 + Cohort: Patient should receive no more than 1 prior systemic chemotherapy regimen.
• Life expectancy ≥ 12 weeks. 7. ECOG PS of 0 or 1 8. Adequate organ and bone marrow function 9. Ability to undergo during screening a tumor biopsy that is adequate for biomarker analysis.

Exclusion Criteria

• Any concurrent chemotherapy, investigational product , biologic, or hormonal therapy for cancer treatment.
• Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
• Major surgical procedure within 21 days prior to the first dose of IP.
• Patients weighing less than 30 kg
• History of leptomeningeal carcinomatosis
• Ascites requiring intervention
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy
• Current or prior use of immunosuppressive medication within 14 days of first dose
• Brain metastases or spinal cord compression.
• Medi4736+AZD5069 Cohort only: received any potent and moderate cytochrome CYP3A4 inhibitors, potent and moderate CYP3A4 inducers, P-gp substrates, BCRP substrates, sensitive CYP2B6 substrates, warfarin and coumarin derivatives, or herbal supplements within 14 days of the first dose of study treatment
• Uncontrolled intercurrent illness
• Other malignancy within 5 years except for noninvasive malignancies
• Mean QT interval ≥470 ms
• Active infection
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
• Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing an effective method of birth control
• Prior exposure to immune-mediated therapy
• Known allergy or hypersensitivity to IP formulations or to other human monoclonal antibodies