A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)

Roche

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Pancreatic Adenocarcinoma

Treatments: Drug: Fluorouracil; Drug: RO6874281; Drug: BL-8040; Drug: Gemcitabine; Drug: Tocilizumab; Drug: PEGPH20; Drug: Atezolizumab; Drug: Tiragolumab; Drug: Nab-Paclitaxel; Drug: Bevacizumab; Drug: Leucovorin; Drug: AB928; Drug: Oxaliplatin; Drug: Cobimetinib; Drug: Selicrelumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03193190

2016-004126-42 (EudraCT Number)

WO39608

Details and patient eligibility

About

A Phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of patients who have received no prior systemic therapy for metastatic PDAC, and Cohort 2 will consist of patients who have received one line of prior systemic therapy for PDAC. In each cohort, eligible patients will be assigned to one of several treatment arms.

Enrollment: 340 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
• For patients in Cohort 1: no prior systemic treatment for PDAC
• For patients in Cohort 2: disease progression during administration of either 5-FU- or gemcitabine-based first-line chemotherapy
• Life expectancy greater than or equal to 3 months
• Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing
• Measurable disease (at least one target lesion) according to RECIST v1.1
• Adequate hematologic and end-organ function test results
• Tumor accessible for biopsy
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Exclusion criteria

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage procedure (i.e., more than one time per month)
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Positive human immunodeficiency (HIV) test at screening or at any time prior to screening
• Active hepatitis B or C virus infection or active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• History of malignancy other than pancreatic carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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340 participants in 12 patient groups

Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)

Active Comparator group

Description:

Cohort 1: Participants will receive Nab-Paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle. Participants in the Cohort 1 control arm who experience disease progression will be given the option of enrolling into Cohort 2 (if open for enrollment), provided they meet eligibility criteria.

Treatment:

Drug: Nab-Paclitaxel

Drug: Gemcitabine

Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab

Experimental group

Description:

Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Selicrelumab 16 mg subcutaneous injection on Day 1 of Cycles 1-4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each 28-day cycle.

Treatment:

Drug: Selicrelumab

Drug: Nab-Paclitaxel

Drug: Atezolizumab

Drug: Gemcitabine

Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab

Experimental group

Description:

Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Bevacizumab 10 mg/kg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Treatment:

Drug: Bevacizumab

Drug: Nab-Paclitaxel

Drug: Atezolizumab

Drug: Gemcitabine

Cohort 1: Atezolizumab + Chemotherapy + AB928

Experimental group

Description:

Cohort 1: Participant will receive AB928 150 mg orally once daily on Days 1 to 28 of each 28 day cycle; Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Treatment:

Drug: AB928

Drug: Nab-Paclitaxel

Drug: Atezolizumab

Drug: Gemcitabine

Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab

Experimental group

Description:

Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Tiragolumab 420 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Treatment:

Drug: Nab-Paclitaxel

Drug: Tiragolumab

Drug: Atezolizumab

Drug: Gemcitabine

Cohort 2: Atezolizumab + Cobimetinib

Experimental group

Description:

Cohort 2: Participants will receive Cobimetinib 60 milligrams (mg) once daily orally on Days 1-21 of each 28-day cycle; and Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28-day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arm is open for enrollment.

Treatment:

Drug: Cobimetinib

Drug: Atezolizumab

Cohort 2: Atezolizumab + PEGPH20

Experimental group

Description:

Cohort 2: Participants will receive PEGPH20 3 micrograms per kilogram (mcg/kg) IV infusion on Days 1, 8 and 15 of each 21-day cycle; and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

Treatment:

Drug: Atezolizumab

Drug: PEGPH20

Cohort 2: Atezolizumab + BL-8040

Experimental group

Description:

Cohort 2: Participants will receive BL-8040 1.25 milligrams per kilogram (mg/kg) subcutaneously (SC) on Days 1-5 of the first week, followed by combination treatment consisting of BL-8040 1.25 mg/kg SC three times a week on non-consecutive days and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

Treatment:

Drug: Atezolizumab

Drug: BL-8040

Cohort 2: Atezolizumab + RO6874281 every 2 weeks

Experimental group

Description:

Cohort 2: Participants will receive Atezolizumab 840 mg IV infusion on days 1 and 15 of each 28 day cycle; RO6874281 will be administered 10 mg by IV infusion on day 1 and 15 mg on days 8, 15, and 22 for cycle 1 (28 day cycle). RO6874281 will be administered 15 mg by IV infusion on days 1 and 15 of each subsequent 28 day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.

Treatment:

Drug: Atezolizumab

Drug: RO6874281

Cohort 2: Atezolizumab + RO6874281 every 3 weeks

Experimental group

Description:

Cohort 2: Participants will receive Atezolizumab 1200 mg IV infusion on Day 1 of each 21 day cycle; and RO6874281 10 mg by IV infusion on day 1 of each 21 day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.

Treatment:

Drug: Atezolizumab

Drug: RO6874281

Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)

Active Comparator group

Description:

Cohort 2: Participants who progressed on a prior fluoropyrimidine-based regimen will receive Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle. Participants who progressed on a prior gemcitabine-based regimen will receive 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6). Participants will receive Oxaliplatin 85 mg/m^2 IV on Days 1 and 15 of each 28 day cycle; Leucovorin 400 mg/m^2 IV on Days 1 and 15 of each 28 day cycle; Fluorouracil 400 mg/m^2 IV push on Days 1 and 15 of each 28 day cycle; and Fluorouracil 2400 mg/m^2 IV continuous infusion over 46 hours on Days 1 and 2 and on Days 15 and 16 of each 28 day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Nab-Paclitaxel

Drug: Gemcitabine

Drug: Fluorouracil

Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab

Experimental group

Description:

Cohort 1: Participants will receive Tocilizumab 8 mg/kg IV infusion on Day 1 of each 28 day cycle; Atezolizumab 1680 mg IV infusion on Day 1 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Treatment:

Drug: Nab-Paclitaxel

Drug: Atezolizumab

Drug: Tocilizumab

Drug: Gemcitabine