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

Phase 2CompletedNCT03193190

Hoffmann-La Roche341 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

341

Conditions

Pancreatic Adenocarcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

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

...and 13 more locations

Outcomes

Primary Outcomes

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.

Time frame: Up to 33.3 months

Secondary Outcomes

Number of Participants With Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Time frame: Up to 33.3 months

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

PFS was defined as the time from study treatment initiation to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (K-M) method was used to estimate PFS.

Time frame: Up to 33.3 months

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

OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS.

Time frame: Up to 33.3 months

Stage 1: OS Rate at Month 6

OS was defined as the time from randomization to death from any cause. OS rate at 6 months was defined as the percentage of participants who did not experience death from any cause at 6 months from randomization. K-M method was used to estimate OS. Percentages have been rounded off.

Time frame: Month 6

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

DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. DOR was calculated for participants who had a best confirmed OR of CR/PR. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate DOR.

Time frame: Up to 33.3 months

Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1

DC was defined as stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1 Disease control rate (DCR) was defined as the percentage of participants with DC. 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 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages have been rounded off.

Time frame: Up to 33.3 months