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.
Name: V941
Description: V941 administered IM, Q3W for 9 3-week cyclesType: BiologicalV941 Monotherapy V941 + Pembrolizumab
Name: Pembrolizumab
Description: Pembrolizumab 200 mg, IV for 35 3-week cyclesType: BiologicalV941 + Pembrolizumab
Description: The following toxicities graded for severity using NCI Common Terminology for Adverse Events (CTCAE), Version 4.0 will be 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 the participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by the investigator.
Measure: Dose-Limiting Toxicities (DLTs) Time: Cycle 1 (Up to 21 days)Description: Number of participants who experienced 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.
Measure: Adverse Events (AEs) Time: Up to approximately 25 monthsDescription: Number of participants who discontinued from study 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.
Measure: Discontinuations Time: Up to approximately 24 monthsDescription: ORR is assessed by the investigator based on Response Rate Assessed by Modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and RECIST for immune-based therapeutics (iRECIST) following administration of V941 in combination with pembrolizumab. Objective response is a confirmed complete response (CR) or partial response (PR).
Measure: Objective Response Rate (ORR) Time: Up to approximately 24 monthsDescription: Presence of and changes in the quantity of mutant KRAS specific T cells in the periphery.
Measure: Mutant KRAS Specific T cells Time: Up to approximately 24 monthsDescription: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.
Measure: T-cell receptor (TCR) Time: Up to approximately 24 monthsAllocation: Non-Randomized
Parallel Assignment
There are 4 SNPs
T-cell receptor (TCR) clonality and diversity in the periphery and tumor.. Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D --- --- G12C ---
Part 2 Only - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit) All - A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. --- G12D --- --- G12V --- --- G13D --- --- G12C ---
Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D --- --- G12C ---
T-cell receptor (TCR) clonality and diversity in the periphery and tumor.. Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D ---
Part 2 Only - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit) All - A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. --- G12D ---
Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D ---
T-cell receptor (TCR) clonality and diversity in the periphery and tumor.. Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V ---
Part 2 Only - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit) All - A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. --- G12D --- --- G12V ---
Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V ---
T-cell receptor (TCR) clonality and diversity in the periphery and tumor.. Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D ---
Part 2 Only - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit) All - A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. --- G12D --- --- G12V --- --- G13D ---
Inclusion Criteria: Part 1 Only - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D ---