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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: zoldonrasib + chemotherapy | Experimental | study drug in combination with Investigator choice chemotherapy (mFFX or GnP) |
|
| Arm B: placebo + chemotherapy | Placebo Comparator | placebo in combination with Investigator choice chemotherapy (mFFX or GnP) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zoldonrasib | Drug | oral tablets |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival (PFS) | 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. | Up to approximately 4 years |
| Overall survival (OS) | OS is defined as the time from randomization until death from any cause. | Up to approximately 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| PFS per blinded independent central review (BICR) | 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. | Up to approximately 4 years |
| Objective response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Revolution Medicines Study Director | Contact | 1-844-2-REVMED | medinfo@revmed.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moffitt Cancer Center | Recruiting | Tampa | Florida | 33612 | United States |
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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.
| Drug |
oral tablets |
|
| Oxaliplatin | Drug | IV infusion |
|
| Leucovorin (Calcium Folinate) | Drug | IV infusion |
|
| 5-Fluorouracil | Drug | IV infusion |
|
| Irinotecan | Drug | IV infusion |
|
| Gemcitabine (GEM) | Drug | IV infusion |
|
| Nab-paclitaxel | Drug | IV infusion |
|
Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by Investigator and BICR. |
| Up to approximately 4 years |
| Duration of response (DOR) | 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. | Up to approximately 4 years |
| Incidence of adverse events (AEs) | Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 | Up to approximately 4 years |
| Changes in vital signs | Number of patients with clinically significant changes in vital signs. | Up to approximately 4 years |
| Changes in clinical laboratory test values | Number of patients with changes from baseline in clinical laboratory test values | Up to approximately 4 years |
| 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 | 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. | Up to approximately 4 years |
| 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 | 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. | Up to approximately 4 years |
| Concentration of zoldonrasib in Arm A | Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits. | Up to Cycle 5 Day 1 (each cycle is 28 days) |
| Piedmont Healthcare | Recruiting | Atlanta | Georgia | 30318 | United States |
|
| University of Chicago Medical Center | Recruiting | Chicago | Illinois | 60637 | United States |
|
| Johns Hopkins University | Recruiting | Baltimore | Maryland | 21287 | United States |
|
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| D000077146 | Irinotecan |
| D000093542 | Gemcitabine |
| C520255 | 130-nm albumin-bound paclitaxel |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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