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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03948763
Recruitment Status : Recruiting
First Posted : May 14, 2019
Last Update Posted : October 22, 2020
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Neoplasms Carcinoma, Non-Small-Cell Lung Pancreatic Neoplasms Colorectal Neoplasms Biological: V941 Biological: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 26, 2019
Estimated Primary Completion Date : November 19, 2026
Estimated Study Completion Date : November 19, 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: V941 Monotherapy
V941(mRNA-5671/V941) administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles
Biological: V941
V941 administered IM, Q3W for 9 3-week cycles
Other Name: mRNA-5671/V941

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

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

Primary Outcome Measures :
  1. Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up to 21 days) ]
    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.

  2. Adverse Events (AEs) [ Time Frame: Up to approximately 25 months ]
    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.

  3. Discontinuations [ Time Frame: Up to approximately 24 months ]
    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.

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
    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).

  2. Mutant KRAS Specific T cells [ Time Frame: Up to approximately 24 months ]
    Presence of and changes in the quantity of mutant KRAS specific T cells in the blood.

Other Outcome Measures:
  1. T-cell receptor (TCR) [ Time Frame: Up to approximately 24 months ]
    T-cell receptor (TCR) clonality and diversity in the periphery and tumor.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03948763

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Contact: Toll Free Number 1-888-577-8839

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United States, California
City of Hope ( Site 1002) Recruiting
Duarte, California, United States, 91010
Contact: Study Coordinator    626-218-3419      
University of California at San Francisco ( Site 1006) Recruiting
San Francisco, California, United States, 94143
Contact: Study Coordinator    415-353-7084      
United States, Connecticut
Smilow Cancer Hospital at Yale New Haven ( Site 1005) Recruiting
New Haven, Connecticut, United States, 06511
Contact: Study Coordinator    203-737-2445      
United States, Tennessee
Sarah Cannon Research Institute ( Site 7000) Recruiting
Nashville, Tennessee, United States, 37203
Contact: Study Coordinator    877-691-7274      
United States, Texas
START San Antonio ( Site 1004) Recruiting
San Antonio, Texas, United States, 78229
Contact: Study Coordinator    210-593-5265      
United States, Washington
Northwest Medical Specialties, PLLC ( Site 1001) Recruiting
Tacoma, Washington, United States, 98405
Contact: Study Coordinator    253-428-8738      
Australia, Victoria
Monash Health-Monash Medical Centre ( Site 6001) Recruiting
Clayton, Victoria, Australia, 3168
Contact: Study Coordinator    +61385722392      
National Cancer Centre Singapore ( Site 3005) Recruiting
Singapore, Central Singapore, Singapore, 169610
Contact: Study Coordinator    +6564368000      
Tan Tock Seng Hospital ( Site 3007) Recruiting
Singapore, Central Singapore, Singapore, 398442
Contact: Study Coordinator    +6563596554      
National University Hospital ( Site 3006) Recruiting
Singapore, Singapore, 119074
Contact: Study Coordinator    +6567724670      
National Cheng Kung University Hospital ( Site 4002) Recruiting
Tainan, Taiwan, 704
Contact: Study Coordinator    +88662353535 x4559      
National Taiwan University Hospital ( Site 4000) Recruiting
Taipei, Taiwan, 10002
Contact: Study Coordinator    +886223123456      
Taipei Veterans General Hospital ( Site 4001) Recruiting
Taipei, Taiwan, 11217
Contact: Study Coordinator    886228757496      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
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Study Director: Medical Director, MD Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT03948763    
Other Study ID Numbers: V941-001
V941-001 ( Other Identifier: Merck Protocol Number )
First Posted: May 14, 2019    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
solid tumors
therapeutic vaccine
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Pancreatic Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents