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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03948763




Registration number
NCT03948763
Ethics application status
Date submitted
10/05/2019
Date registered
14/05/2019
Date last updated
6/05/2021

Titles & IDs
Public title
A Study of mRNA-5671/V941 as Monotherapy and in Combination With Pembrolizumab (V941-001)
Scientific title
A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma
Secondary ID [1] 0 0
V941-001
Secondary ID [2] 0 0
V941-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Carcinoma, Non-Small-Cell Lung 0 0
Pancreatic Neoplasms 0 0
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - V941
Other interventions - Pembrolizumab

Experimental: V941 Monotherapy - V941(mRNA-5671/V941) administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles

Experimental: V941 + Pembrolizumab - V941(mRNA-5671/V941) administered IM Q3W for 9 cycles and pembrolizumab 200 mg, intravenous (IV) for 35 3-week cycles


Other interventions: V941
V941 administered IM, Q3W for 9 3-week cycles

Other interventions: Pembrolizumab
Pembrolizumab 200 mg, IV for 35 3-week cycles

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Limiting Toxicities (DLTs) - 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.
Timepoint [1] 0 0
Cycle 1 (Up to 21 days)
Primary outcome [2] 0 0
Adverse Events (AEs) - 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.
Timepoint [2] 0 0
Up to approximately 25 months
Primary outcome [3] 0 0
Discontinuations - 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.
Timepoint [3] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) - 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).
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
Mutant KRAS Specific T cells - Presence of and changes in the quantity of mutant KRAS specific T cells in the blood.
Timepoint [2] 0 0
Up to approximately 24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre ( Site 6000) - Darlinghurst
Recruitment hospital [2] 0 0
Southern Oncology Clinical Research Unit SOCRU ( Site 6002) - Bedford Park
Recruitment hospital [3] 0 0
Monash Health-Monash Medical Centre ( Site 6001) - Clayton
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Nevada
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Hong Kong
State/province [9] 0 0
Hong Kong
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Singapore
State/province [11] 0 0
Central Singapore
Country [12] 0 0
Taiwan
State/province [12] 0 0
Tainan
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03948763
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03948763