Pancreatic Adenocarcinoma, Pancreatic Adenocarcinoma Metastatic, Pancreatic Adenosquamous Carcinoma, Pancreatic Cancer, Pancreatic Cancer Metastatic, Pancreatic Ductal Adenocarcinoma (PDAC), PDAC, PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, RAS Mutation, Pancreatic Cancer Metastatic, Pancreatic Adenocarcinoma Metastatic, Pancreatic Adenosquamous Carcinoma, Pancreatic Adenocarcinoma
Brief summary
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with chemotherapy.
Detailed description
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator. Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of chemotherapy (Arm B).
Interventions
DRUGZoldonrasib
oral tablets
DRUGPlacebo
oral tablets
DRUGOxaliplatin
IV infusion
IV infusion
DRUG5-Fluorouracil
IV infusion
DRUGIrinotecan
IV infusion
IV infusion
DRUGNab-paclitaxel
IV infusion
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Chemotherapy administration will be open label. This study is double-blind with respect to zoldonrasib versus placebo and treatment assignments will remain blinded to the Investigator, study center staff, patient, Sponsor, and study vendors.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old and has provided informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Histologically or cytologically confirmed pancreatic adenocarcinoma. * Diagnosis of metastatic disease ≤ 6 weeks prior to screening. * Documented KRAS G12D mutation status. * Measurable disease per RECIST v1.1. * Adequate organ function (bone marrow, liver, kidney, coagulation). * Able to take oral medications.
Exclusion criteria
* Prior treatment with systemic anticancer therapy in unresectable locally advanced or metastatic setting. * Prior systemic RAS-targeted therapy any time prior to randomization. * Presence of other known driver mutations with approved targeted therapies * Active or known history of untreated central nervous system metastatic disease. * Any conditions that may affect the ability to take or absorb study drug. * Major surgery within 28 days prior to randomization. * Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to approximately 4 years | PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per response evaluation criteria in solid tumors (RECIST) v1.1 by Investigator. |
| Overall survival (OS) | Up to approximately 4 years | OS is defined as the time from randomization until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS per blinded independent central review (BICR) | Up to approximately 4 years | PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed RECIST v1.1 by BICR. |
| Objective response rate (ORR) | Up to approximately 4 years | Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by Investigator and BICR. |
| Duration of response (DOR) | Up to approximately 4 years | DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by the investigator and BICR. |
| Incidence of adverse events (AEs) | Up to approximately 4 years | Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
| Changes in vital signs | Up to approximately 4 years | Number of patients with clinically significant changes in vital signs. |
| Changes in clinical laboratory test values | Up to approximately 4 years | Number of patients with changes from baseline in clinical laboratory test values |
| Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) pain scale | Up to approximately 4 years | EORTC QLQ-PAN26 consists of 26 questions relating to disease symptoms, treatment side effects and emotional issues specific to pancreatic cancer. The pancreatic pain subscale assesses abdominal pain, back pain, and pain while lying down. Change in score from baseline in the pain subscale will be assessed with higher scores on the pain subscale indicating more severe pain and worsening function. |
| Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score | Up to approximately 4 years | EORTC QLQ-C30 consists of 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties), and an overall scale for global health status. It uses a mix of 4-point scales and 7-point scales. Change from baseline in EORTC QLQ-C30 global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden. |
| Concentration of zoldonrasib in Arm A | Up to Cycle 5 Day 1 (each cycle is 28 days) | Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits. |
Countries
United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed