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

NCT ID: NCT03193190

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 341 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-05
• Study Completion Date: 2025-02-27

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)

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.

Group Type: ACTIVE_COMPARATOR

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab

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.

Group Type: EXPERIMENTAL

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Selicrelumab

Intervention Type: DRUG

Selicrelumab will be administered as per the schedule specified in the respective arm.

Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab

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.

Group Type: EXPERIMENTAL

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered as per the schedule specified in the respective arm.

Cohort 1: Atezolizumab + Chemotherapy + AB928

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.

Group Type: EXPERIMENTAL

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

AB928

Intervention Type: DRUG

AB928 will be administered as per the schedule specified in the respective arm.

Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab

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.

Group Type: EXPERIMENTAL

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Tiragolumab

Intervention Type: DRUG

Tiragolumab will be administered as per the schedule specified in the respective arm.

Cohort 2: Atezolizumab + Cobimetinib

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Cobimetinib

Intervention Type: DRUG

Cobimetinib will be administered as per the schedule specified in the respective arm.

Cohort 2: Atezolizumab + PEGPH20

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arm.

Cohort 2: Atezolizumab + BL-8040

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

BL-8040

Intervention Type: DRUG

BL-8040 will be administered as per the schedule specified in the respective arm.

Cohort 2: Atezolizumab + RO6874281 every 2 weeks

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

RO6874281

Intervention Type: DRUG

RO6874281 will be administered as per the schedule specified in the respective arm

Cohort 2: Atezolizumab + RO6874281 every 3 weeks

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

RO6874281

Intervention Type: DRUG

RO6874281 will be administered as per the schedule specified in the respective arm

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

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.

Group Type: ACTIVE_COMPARATOR

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin will be administered as per the schedule specified in the respective arm.

Leucovorin

Intervention Type: DRUG

Leucovorin will be administered as per the schedule specified in the respective arm.

Fluorouracil

Intervention Type: DRUG

Fluorouracil will be administered as per the schedule specified in the respective arm.

Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab

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.

Group Type: EXPERIMENTAL

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as per the schedule specified in the respective arm.

Interventions

Nab-Paclitaxel

Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Gemcitabine

Gemcitabine will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Leucovorin

Leucovorin will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Fluorouracil

Fluorouracil will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Cobimetinib

Cobimetinib will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

PEGPH20

PEGPH20 will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

BL-8040

BL-8040 will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Selicrelumab

Selicrelumab will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

RO6874281

RO6874281 will be administered as per the schedule specified in the respective arm

Intervention Type: DRUG

AB928

AB928 will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Tiragolumab

Tiragolumab will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Tocilizumab

Tocilizumab will be administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Helen Diller Fam Comp Can Ctr

San Francisco, California, United States

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, United States

Uni of Chicago Medical Center

Chicago, Illinois, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

MorristownMedicalCenter

Morristown, New Jersey, United States

Columbia University

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Universitätsklinikum Essen

Essen, , Germany

National Cancer Center Hospital East

Chiba, , Japan

Kanagawa Cancer Center

Kanagawa, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Hosp. G. U Gregorio Marañón

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Countries

United States; Germany; Japan; South Korea; Spain

References

Ko AH, Kim KP, Siveke JT, Lopez CD, Lacy J, O'Reilly EM, Macarulla T, Manji GA, Lee J, Ajani J, Alsina Maqueda M, Rha SY, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh CS, Gan X, Cha E, Oh DY. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.

Reference Type: DERIVED

PMID: 36940261 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-004126-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO39608

Identifier Type: -

Identifier Source: org_study_id