Clinical trial NCT02583477: Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma
Official title: A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: Pancreatic Ductal Adenocarcinoma, PDAC, immunotherapy, PDL1, AZD5069, MEDI4736
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-10-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Cohort 1: From time of first dose of MEDI4736 on Day 1 up to Day 28 of Cycle 1 and Cohort 2: From time of first dose of AZD5069 and MEDI4736 on Day 1 up to Day 28 of Cycle 1 or until a participant experiences a DLT, whichever occurs first.
measure: Number of Participants With AEs
timeFrame: From first dose of study treatment administration (Day 1) until 90 days after the last dose of IP or initiation of the first subsequent anticancer therapy (whichever occurred first), approximately 30 months.
measure: Objective Response Rate (ORR) in Cohort 2
timeFrame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
Secondary outcomes:
measure: Duration of Response (DoR) in Cohort 2
timeFrame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
measure: Disease Control Rate (DCR) in Cohort 2
timeFrame: RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days for first 48 weeks up to 6 months and 12 months
measure: Median Progression-Free Survival (PFS) in Cohort 2
timeFrame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
measure: Progression-Free Survival Rate at 3 Months (PFS3) in Cohort 2
timeFrame: RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days up to 3 months
measure: Progression-Free Survival Rate at 6 Months (PFS6) in Cohort 2
timeFrame: RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days up to 6 months
measure: Median Overall Survival (OS) in Cohort 2
timeFrame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
measure: Overall Survival at 6 Months (OS6) in Cohort 2
timeFrame: From first dose of study treatment (Day 1) up to 6 months
measure: Overall Survival at 12 Months (OS12) in Cohort 2
timeFrame: From first dose of study treatment (Day 1) up to 12 months
measure: Number of Participants With Anti-Drug Antibody (ADAs) for MEDI4736 in Cohort 2
timeFrame: On Day 1 of Cycles 1, 2, 3, 4, and 7; At months 3 and 6 after last dose
measure: Mean Plasma Concentrations of MEDI4736 in Cohort 2
timeFrame: Predose (within 60 minutes prior to treatment with any IP) on Day 1 of Cycles 1, 2, 3, 4, and 7; and post infusion (within 10 minutes after end of MEDI4736 infusion) on Day 1 of Cycles 1 and 7
measure: Mean Plasma Concentrations of AZD5069 in Cohort 2
timeFrame: Predose (within 60 minutes prior to treatment with any IP) on Day 1 of Cycles 1, 2, 3, 4, and 7; and postdose (within 10 minutes after end of MEDI4736 infusion) on Day 1 of Cycles 1, 2, and 7
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Research Site
state: New York
city: Cambridge
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Beatson Institute, University of Glasgow, Garscrube Estate, Switchback Rd. Glasgow, UK, G61 1BD
name: Jeff Evans, M.D
role: PRINCIPAL_INVESTIGATOR
References: