A Phase 3, Double-blind, Placebo-controlled, Randomized Study to Assess the Efficacy and Safety of ASP3082 in Combination With mFOLFIRINOX or NALIRIFOX as First-line Treatment in Participants With KRAS G12D Mutated Metastatic Pancreatic Adenocarcinoma
Summary
Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. The first treatment that people usually receive is chemotherapy. At the time this study started, some of the main standard chemotherapies for pancreatic cancer were mFOLFIRINOX or NALIRIFOX. Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with pancreatic cancer have a faulty KRAS gene. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation. This study is about setidegrasib given with chemotherapy in people with pancreatic cancer who have the KRAS G12D mutation. Before setidegrasib can become an approved treatment, clinical studies need to be completed to understand how it works and how safe it is. The main aim is to learn if people who are given setidegrasib with chemotherapy live for longer than people who are given placebo with chemotherapy. Other aims are to learn if setidegrasib delays the cancer and symptoms returning, how the body processes setidegrasib, and its safety, when given with chemotherapy. People in this study will be adults with metastatic pancreatic cancer with the G12D mutation in their KRAS gene. Surgery or radiotherapy will not be an option to cure their cancer. People cannot take part if the cancer cells have spread to the thin tissue covering the brain and spinal cord (leptomeningeal disease), have symptoms of cancer in the brain or nervous system, or have recently had some other cancers that required treatment. In this study, people are given either setidegrasib with mFOLFIRINOX or NALIRIFOX chemotherapy, or a placebo with mFOLFIRINOX or NALIRIFOX chemotherapy. Whether people receive setidegrasib or placebo is decided by chance. The study doctor decides which chemotherapy (mFOLFIRINOX or NALIRIFOX) people receive. People will only receive NALIRIFOX chemotherapy (with ASP3082 or placebo) after the safety of ASP3082 with NALIRIFOX chemotherapy has been confirmed in another ongoing ASP3082 study. All of the study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly they pass away. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study.
Arms & interventions
- DrugSetidegrasib
Intravenous infusion
- DrugOxaliplatin
Intravenous infusion
- DrugLeucovorin
Intravenous infusion
- DrugIrinotecan
Intravenous infusion
- Drugfluorouracil
Intravenous infusion
- Drugliposomal irinotecan
Intravenous infusion
- DrugPlacebo
Intravenous Infusion
Outcome measures
Primary
Overall Survival (OS)
OS is defined as the time from the date of randomization until the date of death from any cause.
Time frame: Up to 3.5 years
Secondary
Progression-Free Survival (PFS) per RECIST v1.1. as assessed by the investigator.
Time frame: Up to 3.5 years
Time to Improvement in Pancreatic Pain (TIPP) measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PAN26).
Time frame: Up to 3.5 years
Time to Worsening of General Health Status/Quality of Life (GHS/QoL) (TWGQ) measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Time frame: Up to 3.5 years
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1,
Time frame: Up to 3.5 years
Number of Participants with Adverse Events (AEs)
Time frame: Up to 3.5 years
Number of Participants with Serious Adverse Events (SAEs)
Time frame: Up to 3.5 years
Number of Participants with laboratory value abnormalities and/or AEs
Time frame: Up to 3.5 years
Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs.
Time frame: Up to 3.5 years
Number of Participants with vital sign abnormalities and/or AEs.
Time frame: Up to 3.5 years
Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status.
Time frame: Up to 3.5 years
Pharmacokinetics (PK) of setidegrasib End-of-Infusion (EOI) concentration
Time frame: Up to 9 months
PK of setidegrasib in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
Time frame: Up to 9 months
Change from baseline in EORTC QLQ-PAN26
Time frame: Up to 3.5 years
Change from baseline in EORTC QLQ-C30
Time frame: Up to 3.5 years
Change from baseline in EuroQol 5-dimensional 5-level version (EQ-5D-5L)
Time frame: Up to 3.5 years
Change from baseline in Patient Global Impression of Change (PGIC).
Time frame: Up to 3.5 years
Change from baseline in Patient Global Impression of Severity PGIS
Time frame: Up to 3.5 years
Eligibility criteria
Study locations (14)
Crosson Cancer Institute at Providence St. Jude Medical Center in Fullerton
Fullerton, California, 92835
Hoag Mem Hosp Presbyterian
Newport Beach, California, 92663
Baptist MD Anderson Cancer Institute
Jacksonville, Florida, 32207
Saint Elizabeth Medical Center, Inc. DBA St. Elizabeth Health Care
Edgewood, Kentucky, 41017
HealthPartners Frauenshuh Cancer Center
Saint Louis Park, Minnesota, 55426
HealthPartners Cancer Center at Regions Hospital
Saint Paul, Minnesota, 55101
NYU Long Island Mineola
Mineola, New York, 11501
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
White Plains Hospital Center for Cancer Care - Oncology
White Plains, New York, 10601
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390
Utah Cancer Specialists
Salt Lake City, Utah, 84106
UVA Emily Couric Cancer Center
Charlottesville, Virginia, 22903
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Virginia Mason Franciscan Health - Virginia Mason Medical Center
Seattle, Washington, 98101