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

A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations (with chemotherapy or AZD5069) in Patients with Metastatic Pancreatic Ductal Adenocarcinoma

This is a Phase Ib and II open-label, multi-center study to evaluate the safety, tolerability, pharmacodynamics, and antitumor activity of MEDI4736 in combination with chemotherapy or AZD5069 in patients with pancreatic ductal adenocarcinoma (PDAC). This study will consist of 2 independent cohorts.

Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic PDAC, no more than 1 prior chemotherapy regimen or treatment-naïve patients
2. Eastern Cooperative Oncology Group 0 or 1
3. 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
4. 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.

6. 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:

1. Any concurrent chemotherapy, investigational product , biologic, or hormonal therapy for cancer treatment.
2. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
3. Major surgical procedure within 21 days prior to the first dose of IP.
4. Patients weighing less than 30 kg
5. History of leptomeningeal carcinomatosis
6. Ascites requiring intervention
7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy
8. Current or prior use of immunosuppressive medication within 14 days of first dose
9. Brain metastases or spinal cord compression.
10. 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
11. Uncontrolled intercurrent illness
12. Other malignancy within 5 years except for noninvasive malignancies
13. Mean QT interval ≥470 ms
14. Active infection
15. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
16. 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
17. Prior exposure to immune-mediated therapy
18. Known allergy or hypersensitivity to IP formulations or to other human monoclonal antibodies