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
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.
- 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)
- 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
- 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
- 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
- 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
- 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.