NCT03948763 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-01-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Dose-Limiting Toxicities (DLTs)

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outcome · POSTED

Number of Participants Who Experienced an Adverse Event (AE)

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outcome · POSTED

Number of Participants Who Discontinued Study Treatment Due to an AE

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells

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outcome · POSTED

Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells

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outcome · POSTED

T-cell Receptor (TCR) Clonality and Diversity

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: Part 2 Only \- Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), non-mismatch repair deficient/microsatellite instability-high tumors colorectal cancers (non-MSI-H CRC), or pancreatic adenocarcinoma, and confirmed HLA types HLA-A11:01 and/or HLA C08:02 (and/or potentially other additional HLA types to be specified). NSCLC: Participants must have been tested for mutations affecting EGFR and/or anaplastic lymphoma kinase (ALK). Participants with ALK or epidermal growth factor receptor (EGFR)-positive NSCLC must have had recurrent or progressive disease (PD) after treatment with the corresponding inhibitor and current standard of care, in any sequence. Non-MSI-H CRC: Participant tumors must have been locally tested for MSI and have been found to be non-MSI-H. All * 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. Exclusion Criteria: * 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
V941(mRNA-5671/V941) 1 mg administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles
intervention Names
Biological: V941
label
Part 1: V941 Monotherapy
type
EXPERIMENTAL
description
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
intervention Names
Biological: V941
Biological: Pembrolizumab
label
Part 1: V941 + Pembrolizumab
type
EXPERIMENTAL
description
V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles
intervention Names
Biological: V941
Biological: Pembrolizumab
label
Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab)
type
EXPERIMENTAL
description
V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles
intervention Names
Biological: V941
Biological: Pembrolizumab
label
Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab)
type
EXPERIMENTAL
description
V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles
intervention Names
Biological: V941
Biological: Pembrolizumab
label
Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab)
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1: V941 + Pembrolizumab
Part 1: V941 Monotherapy
Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab)
Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab)
Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab)
description
V941 administered IM, Q3W for 9 3-week cycles
name
V941
other Names
mRNA-5671/V941
type
BIOLOGICAL
arm Group Labels
Part 1: V941 + Pembrolizumab
Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab)
Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab)
Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab)
description
Pembrolizumab 200 mg, IV for 35 3-week cycles
name
Pembrolizumab
other Names
MK-3475
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 70
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
TCR clonality and diversity in the periphery and tumor.
measure
T-cell Receptor (TCR) Clonality and Diversity
time Frame
Up to approximately 24 months

primary Outcomes

description
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.
measure
Dose-Limiting Toxicities (DLTs)
time Frame
Cycle 1 (Up to 21 days)
description
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
Number of Participants Who Experienced an Adverse Event (AE)
time Frame
Up to approximately 27 months
description
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.
measure
Number of Participants Who Discontinued Study Treatment Due to an AE
time Frame
Up to approximately 24 months

secondary Outcomes

description
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.
measure
Objective Response Rate (ORR)
time Frame
Up to approximately 24 months
description
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.
measure
Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells
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)
description
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.
measure
Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells
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)

Full study description

brief Summary: 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.

Source references