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

Study Overview

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

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.

N/A

Pancreatic Adenocarcinoma

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

WO39608
2016-004126-42 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-06-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-17
First Submitted that Met QC Criteria 2017-06-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-18
First Posted (ACTUAL) 2017-06-20	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: 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 experienc
EXPERIMENTAL: 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	DRUG: Nab-Paclitaxel Nab-Paclitaxel will be administered as per the schedule specified in the respective arm. DRUG: Gemcitabine Gemcitabine will be administered as per the schedule specified in the respective arm. DRUG: Atezolizumab Atezolizumab will be administered as per the schedule specified in the respective arm. DRUG: Selicrelumab Selicrelumab will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 cy	DRUG: Nab-Paclitaxel Nab-Paclitaxel will be administered as per the schedule specified in the respective arm. DRUG: Gemcitabine Gemcitabine will be administered as per the schedule specified in the respective arm. DRUG: Atezolizumab Atezolizumab will be administered as per the schedule specified in the respective arm. DRUG: Bevacizumab Bevacizumab will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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;	DRUG: Nab-Paclitaxel Nab-Paclitaxel will be administered as per the schedule specified in the respective arm. DRUG: Gemcitabine Gemcitabine will be administered as per the schedule specified in the respective arm. DRUG: Atezolizumab Atezolizumab will be administered as per the schedule specified in the respective arm. DRUG: AB928 AB928 will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 cycl	DRUG: Nab-Paclitaxel Nab-Paclitaxel will be administered as per the schedule specified in the respective arm. DRUG: Gemcitabine Gemcitabine will be administered as per the schedule specified in the respective arm. DRUG: Atezolizumab Atezolizumab will be administered as per the schedule specified in the respective arm. DRUG: Tiragolumab Tiragolumab will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 optio	DRUG: Cobimetinib Cobimetinib will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 th	DRUG: PEGPH20 PEGPH20 will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 Atezol	DRUG: BL-8040 BL-8040 will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 administe	DRUG: RO6874281 RO6874281 will be administered as per the schedule specified in the respective arm
EXPERIMENTAL: 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 +	DRUG: RO6874281 RO6874281 will be administered as per the schedule specified in the respective arm
ACTIVE_COMPARATOR: 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	DRUG: Oxaliplatin Oxaliplatin will be administered as per the schedule specified in the respective arm. DRUG: Leucovorin Leucovorin will be administered as per the schedule specified in the respective arm. DRUG: Fluorouracil Fluorouracil will be administered as per the schedule specified in the respective arm.
EXPERIMENTAL: 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 Gemcita	DRUG: Nab-Paclitaxel Nab-Paclitaxel will be administered as per the schedule specified in the respective arm. DRUG: Gemcitabine Gemcitabine will be administered as per the schedule specified in the respective arm. DRUG: Atezolizumab Atezolizumab will be administered as per the schedule specified in the respective arm. DRUG: Tocilizumab Tocilizumab will be administered as per the schedule specified in the respective arm.

Primary Outcome Measures	Measure Description	Time Frame
Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)		From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)
Percentage of Participants With Adverse Events (AEs)		From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 7-9 years)

Secondary Outcome Measures	Measure Description	Time Frame
Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1		From randomization up to the first occurrence of disease (up to approximately 7-9 years)
Overall Survival		From randomization up to death from any cause (up to approximately 7-9 years)
Percentage of Participants who are Alive at Month 6		Month 6
Duration of Response, as Determined by Investigator According to RECIST v1.1		From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 7-9 years)
Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1		From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Clinical Trials, Hoffmann-La Roche

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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