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

NCT03193190 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: WO396082016-004126-42
• Study Type: interventional
• Target: 341
• Locations: 5 countries
• Sites: 23

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

Outcome Measures

Primary Outcomes (1)

• Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart during Stage 1 as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.

  Up to 33.3 months

Secondary Outcomes (6)

• Number of Participants With Adverse Events (AEs)

  Up to 33.3 months

• Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1

  Up to 33.3 months

• Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1

  Up to 33.3 months

• Stage 1: OS Rate at Month 6

  Month 6

• Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1

  Up to 33.3 months

Study Arms (12)

Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)

ACTIVE COMPARATOR

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine

Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab

EXPERIMENTAL

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Selicrelumab

Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab

EXPERIMENTAL

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Bevacizumab

Cohort 1: Atezolizumab + Chemotherapy + AB928

EXPERIMENTAL

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Atezolizumab; Drug: AB928

Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab

EXPERIMENTAL

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Tiragolumab

Cohort 2: Atezolizumab + Cobimetinib

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Cobimetinib

Cohort 2: Atezolizumab + PEGPH20

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: PEGPH20

Cohort 2: Atezolizumab + BL-8040

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: BL-8040

Cohort 2: Atezolizumab + RO6874281 every 2 weeks

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6874281

Cohort 2: Atezolizumab + RO6874281 every 3 weeks

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6874281

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

ACTIVE COMPARATOR

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab

EXPERIMENTAL

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.

Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Tocilizumab

Interventions

Nab-Paclitaxel DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + AB928; Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab; Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab; Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab; Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab; Cohort 1: Control (Nab-Paclitaxel and Gemcitabine); Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)

Gemcitabine DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + AB928; Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab; Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab; Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab; Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab; Cohort 1: Control (Nab-Paclitaxel and Gemcitabine); Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)

Oxaliplatin DRUG

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

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

Leucovorin DRUG

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

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

Fluorouracil DRUG

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

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

Atezolizumab DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + AB928; Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab; Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab; Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab; Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab; Cohort 2: Atezolizumab + BL-8040; Cohort 2: Atezolizumab + Cobimetinib; Cohort 2: Atezolizumab + PEGPH20; Cohort 2: Atezolizumab + RO6874281 every 2 weeks; Cohort 2: Atezolizumab + RO6874281 every 3 weeks

Cobimetinib DRUG

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

Cohort 2: Atezolizumab + Cobimetinib

PEGPH20 DRUG

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

Cohort 2: Atezolizumab + PEGPH20

BL-8040 DRUG

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

Cohort 2: Atezolizumab + BL-8040

Selicrelumab DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab

Bevacizumab DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab

RO6874281 DRUG

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

Cohort 2: Atezolizumab + RO6874281 every 2 weeks; Cohort 2: Atezolizumab + RO6874281 every 3 weeks

AB928 DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + AB928

Tiragolumab DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab

Tocilizumab DRUG

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

Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Helen Diller Fam Comp Can Ctr

San Francisco, California, 94158, United States

Location

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510, United States

Location

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Uni of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MorristownMedicalCenter

Morristown, New Jersey, 07962, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Vall d Hebron

Barcelona, 08035, Spain

Location

Hosp. G. U Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28037, Spain

Location

Related Publications (1)

• 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.

  PMID: 36940261 DERIVED

MeSH Terms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine; Oxaliplatin; Leucovorin; Fluorouracil; atezolizumab; cobimetinib; PEGPH20; 4-fluorobenzoyl-TN-14003; selicrelumab; Bevacizumab; Tiragolumab; tocilizumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 20, 2017
• Study Start: July 5, 2017
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Locations

JP (3); KR (3); DE (1); ES (4); US (12)