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

Pancreatic Adenocarcinoma Clinical Trial

Official title:

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03193190
• Other study ID #: WO39608
• Secondary ID: 2016-004126-42
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 5, 2017
• Est. completion date: October 31, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 340
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma

Intervention

Drug:
• Nab-Paclitaxel
Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
• Gemcitabine
Gemcitabine will be administered as per the schedule specified in the respective arm.
• Oxaliplatin
Oxaliplatin will be administered as per the schedule specified in the respective arm.
• Leucovorin
Leucovorin will be administered as per the schedule specified in the respective arm.
• Fluorouracil
Fluorouracil will be administered as per the schedule specified in the respective arm.
• Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
• Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
• PEGPH20
PEGPH20 will be administered as per the schedule specified in the respective arm.
• BL-8040
BL-8040 will be administered as per the schedule specified in the respective arm.
• Selicrelumab
Selicrelumab will be administered as per the schedule specified in the respective arm.
• Bevacizumab
Bevacizumab will be administered as per the schedule specified in the respective arm.
• RO6874281
RO6874281 will be administered as per the schedule specified in the respective arm
• AB928
AB928 will be administered as per the schedule specified in the respective arm.
• Tiragolumab
Tiragolumab will be administered as per the schedule specified in the respective arm.
• Tocilizumab
Tocilizumab will be administered as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung	Essen
Japan	National Cancer Center Hospital East	Chiba
Japan	Kanagawa Cancer Center	Kanagawa
Japan	National Cancer Center Hospital	Tokyo
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	Hosp. G. U Gregorio Marañón	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Uni of Chicago Medical Center; Room M454	Chicago	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Sarah Cannon Research Institute / Tennessee Oncology	Germantown	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Hillman Cancer Center;Medical Oncology	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Helen Diller Fam Comp Can Ctr	San Francisco	California
United States	Lombardi Cancer Center, Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	Overall Survival		From randomization up to death from any cause (up to approximately 7-9 years)
Secondary	Percentage of Participants who are Alive at Month 6		Month 6
Secondary	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)
Secondary	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)