A Study Of MRNA-5671/V941 As Monotherapy And In Combination With Pembrolizumab (V941-001)

Study Overview

A Study of mRNA-5671/V941 as Monotherapy and in Combination With Pembrolizumab (V941-001)

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.

N/A

Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Colorectal Neoplasms

BIOLOGICAL: V941
BIOLOGICAL: Pembrolizumab

V941-001
V941-001 (OTHER Identifier) (OTHER: MSD Protocol Number)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-05-10	Results First Submitted 2024-08-21	Last Update Submitted that met QC Criteria 2025-01-08
First Submitted that Met QC Criteria 2019-05-10	Results First Submitted that Met QC Criteria 2025-01-08	Last Update Posted (ACTUAL) 2025-01-28
First Posted (ACTUAL) 2019-05-14	Results First Posted 2025-01-28	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part 1: V941 Monotherapy V941(mRNA-5671/V941) 1 mg administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles	BIOLOGICAL: V941 V941 administered IM, Q3W for 9 3-week cycles
EXPERIMENTAL: Part 1: V941 + Pembrolizumab V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, intravenous (IV) for 35 3-week cycles	BIOLOGICAL: V941 V941 administered IM, Q3W for 9 3-week cycles BIOLOGICAL: Pembrolizumab Pembrolizumab 200 mg, IV for 35 3-week cycles
EXPERIMENTAL: Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles	BIOLOGICAL: V941 V941 administered IM, Q3W for 9 3-week cycles BIOLOGICAL: Pembrolizumab Pembrolizumab 200 mg, IV for 35 3-week cycles
EXPERIMENTAL: Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles	BIOLOGICAL: V941 V941 administered IM, Q3W for 9 3-week cycles BIOLOGICAL: Pembrolizumab Pembrolizumab 200 mg, IV for 35 3-week cycles
EXPERIMENTAL: Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles	BIOLOGICAL: Pembrolizumab Pembrolizumab 200 mg, IV for 35 3-week cycles

Primary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	Up to approximately 24 months

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	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.	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.	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)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor identified by local laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit.
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.
A female participant was not be pregnant, not breastfeeding, and at not be a woman of childbearing potential (WOCBP) OR if a WOCBP, agrees to follow study-approved contraceptive guidance during treatment period and for at least 120 days after the last dose of study intervention.
Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
For Part 1 only: Cutaneous lesions can be considered in addition to imaging, but measurable disease should be defined by radiologic assessment.
Have an evaluable archival tumor sample to submit for analysis. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
Have adequate organ function
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
Has an active infection requiring therapy.
Has a history of interstitial lung disease.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy.
Has not fully recovered from any effects of major surgery or has evidence of detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered.
Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, non-cytotoxic small molecule therapeutics within 5 half-lives (or 2 weeks, whichever is longer) prior to the first dose of study treatment, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related adverse events).
Has received a live-virus vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
Has received hematopoietic colony-stimulating growth factors (eg, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, macrophage colony stimulating factor) within 2 weeks prior to the first dose of study intervention.
Discontinued from therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR; eg, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD137 (4-1BB, Tumor necrosis factor-receptor superfamily 9 [TNFSF9]), and OX 40 (TNFRSF4), due to a Grade 3 or higher immune-related adverse event (irAE).
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study intervention.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected) infection.
Has a known history of HIV.
Has a known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
Has had an allogenic tissue/solid organ transplant.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

ModernaTX, Inc.

Investigators

STUDY_DIRECTOR: Medical Director, Merck Sharp and Dohme LLC

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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