Clinical trial NCT03611556: MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.
Official title: A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) With or Without Durvalumab in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma
Metastatic Pancreatic Adenocarcinoma
Keywords: MEDI9447
oleclumab
immunotherapy
pancreatic cancer
durvalumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2018-08-02
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in participants with metastatic pancreatic cancer.

Detailed description: This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to assess the safety, preliminary antitumor activity, immunogenicity, and pharmacokinetics (PK) of oleclumab with or without durvalumab in combination with chemotherapy administered in participants with metastatic pancreatic ductal adenocarcinoma (PDAC). Participants with previously untreated metastatic PDAC (first-line \[1L\] metastatic PDAC) will be enrolled in Cohort A. Participants with metastatic PDAC previously treated with gemcitabine-based chemotherapy (without exposure to 5-fluorouracil \[5-FU\], capecitabine, or oxaliplatin; second-line \[2L\] metastatic PDAC) will be enrolled in Cohort B. The study consists of 2 parts, dose escalation (Part 1) and dose expansion (Part 2).

Eligibility criteria: Inclusion Criteria:

1. Age \>= 18
2. Written and signed informed consent must be obtained
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
4. Weight \>= 35 kg
5. Participants must have histologically or cytologically, confirmed pancreatic adenocarcinoma:

   Cohort A: Participants with previously untreated metastatic pancreatic adenocarcinoma (1L metastatic disease) not previously treated with systemic therapies Cohort B: Participants with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2L metastatic disease
6. Participants must have at least 1 measurable lesion according to RECIST v1.1
7. All Participants must consent to providing archival tumor specimens.

Exclusion Criteria:

1. Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment.
2. Prior receipt of any immune-related therapy
3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
4. Participants with a history of venous thrombosis within the past 3 months
5. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment
6. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
7. Other invasive malignancy within 2 years
8. Any history of leptomeningeal disease or cord compression
9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase
timeFrame: Day 1 through 65.7 weeks (maximum observed duration)
measure: Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase
timeFrame: From Day 1 to 28 days after the first dose of study drugs
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase
timeFrame: Day 1 through 65.7 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase
timeFrame: Day 1 through 65.7 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase
timeFrame: Day 1 through 65.7 weeks (maximum observed duration)
measure: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcomes:
measure: Number of Participants With TEAEs and TESAEs in Dose Expansion Phase
timeFrame: Day 1 through 172.1 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase
timeFrame: Day 1 through 172.1 weeks (maximum observed duration)
measure: Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase
timeFrame: Day 1 through 172.1 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase
timeFrame: Day 1 through 172.1 weeks (maximum observed duration)
measure: Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase
timeFrame: Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
measure: Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase
timeFrame: Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
measure: Number of Participants With Overall Survival Events in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
measure: Overall Survival in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
measure: Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
measure: Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
measure: Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
timeFrame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab
timeFrame: Day 1 through 172.1 weeks (Pre-dose on Cycle [C] 1 Day [D] 1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of oleclumab)
measure: Number of Participants With Positive ADA to Durvalumab
timeFrame: Day 1 through 128 weeks (Pre-dose on C1D1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of durvalumab)
measure: Serum Concentrations of Oleclumab
timeFrame: Ten minutes (mins) (± 5 mins) post end of infusion (EOI), approximately 1 hour (+ 15 mins) after start of infusion on C1D1, C3D1, and C5D1; and pre-dose on C3D1 and C5D1
measure: Serum Concentrations of Durvalumab
timeFrame: Ten mins (± 5 mins) post EOI, approximately 1 hour (+ 15 mins) after start of infusion on C1D1 and C5D1; and pre-dose on C2D1 and C5D1
measure: Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)
timeFrame: Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
measure: Plasma Concentrations of Nab-paclitaxel
timeFrame: Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Blacktown
country: Australia
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Fuenlabrada
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
Study officials:
References: