MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

MedImmune

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Pancreatic Adenocarcinoma; Carcinoma

Treatments: Drug: Nab-paclitaxel; Drug: Oxaliplatin; Drug: Gemcitabine; Drug: Oleclumab; Drug: 5-FU; Drug: Durvalumab; Drug: Folinic acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT03611556

D6070C00005 (Other Grant/Funding Number)

2018-001028-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 213 patients

Sex: All

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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213 participants in 7 patient groups

Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Experimental group

Description:

Participants with 1L metastatic disease will receive intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Durvalumab

Drug: Gemcitabine

Drug: Oleclumab

Drug: Nab-paclitaxel

Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Experimental group

Description:

Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Durvalumab

Drug: Gemcitabine

Drug: Oleclumab

Drug: Nab-paclitaxel

Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX

Experimental group

Description:

Participants with 2L metastatic disease will receive IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Folinic acid

Drug: Durvalumab

Drug: 5-FU

Drug: Oleclumab

Drug: Oxaliplatin

Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX

Experimental group

Description:

Participants with 2L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Folinic acid

Drug: Durvalumab

Drug: 5-FU

Drug: Oleclumab

Drug: Oxaliplatin

Dose-expansion, Gemcitabine + nab-paclitaxel

Active Comparator group

Description:

Participants with 1L metastatic disease will receive IV infusions of chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Gemcitabine

Drug: Nab-paclitaxel

Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel

Experimental group

Description:

Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Gemcitabine

Drug: Oleclumab

Drug: Nab-paclitaxel

Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Experimental group

Description:

Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Treatment:

Drug: Durvalumab

Drug: Gemcitabine

Drug: Oleclumab

Drug: Nab-paclitaxel