This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of V941(mRNA-5671/V941) as a monotherapy and in combination with pembrolizumab infusion.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
V941 administered IM, Q3W for 9 3-week cycles
Pembrolizumab 200 mg, IV for 35 3-week cycles
Dose-Limiting Toxicities (DLTs)
The following toxicities graded for severity using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), were considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by investigator.
Time frame: Cycle 1 (Up to 21 days)
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to approximately 27 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to approximately 24 months
Objective Response Rate (ORR)
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Banner MD Anderson Cancer Center ( Site 1008)
Gilbert, Arizona, United States
City of Hope ( Site 1002)
Duarte, California, United States
University of California at San Francisco ( Site 1006)
San Francisco, California, United States
Smilow Cancer Hospital at Yale New Haven ( Site 1005)
New Haven, Connecticut, United States
Dana-Farber Cancer Institute (Boston) ( Site 1007)
Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada ( Site 1012)
Las Vegas, Nevada, United States
Tennessee Oncology Nashville Drug Development Unit ( Site 7000)
Nashville, Tennessee, United States
START San Antonio ( Site 1004)
San Antonio, Texas, United States
Baylor Scott & White Medical Center - Temple ( Site 1009)
Temple, Texas, United States
Northwest Medical Specialties, PLLC ( Site 1001)
Tacoma, Washington, United States
...and 16 more locations
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by investigator is reported.
Time frame: Up to approximately 24 months
Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells
The presence of mutant KRAS specific T cells (G12D, G12V, G13D, G12C, and Wild type) in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The post-treatment ELISpot readout for a cycle is reported. A cycle is 3 weeks.
Time frame: Cycle 1 - Cycle 9 (a cycle is 3 weeks) and at the Discontinuation Visit (at the time of withdrawal or up to 30 weeks, whichever occurs first)
Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells
Mean change from baseline in the quantity of mutant KRAS specific T cells in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The mean change is reported.
Time frame: Baseline and Cycle 1 - Cycle 9 (a cycle is 3 weeks) and at the Discontinuation Visit (at the time of withdrawal or up to 30 weeks, whichever occurs first)