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

NCT ID: NCT03948763

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-26
• Study Completion Date: 2022-08-25

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: V941 Monotherapy

V941(mRNA-5671/V941) 1 mg administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles

Group Type: EXPERIMENTAL

V941

Intervention Type: BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

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

Group Type: EXPERIMENTAL

V941

Intervention Type: BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab 200 mg, IV for 35 3-week cycles

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

Group Type: EXPERIMENTAL

V941

Intervention Type: BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab 200 mg, IV for 35 3-week cycles

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

Group Type: EXPERIMENTAL

V941

Intervention Type: BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab 200 mg, IV for 35 3-week cycles

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

Group Type: EXPERIMENTAL

V941

Intervention Type: BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab 200 mg, IV for 35 3-week cycles

Interventions

V941

V941 administered IM, Q3W for 9 3-week cycles

Intervention Type: BIOLOGICAL

Pembrolizumab

Pembrolizumab 200 mg, IV for 35 3-week cycles

Intervention Type: BIOLOGICAL

Other Intervention Names

mRNA-5671/V941; MK-3475

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ModernaTX, Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp and Dohme LLC

Locations

Banner MD Anderson Cancer Center ( Site 1008)

Gilbert, Arizona, United States

City of Hope ( Site 1002)

Duarte, California, United States

University of California at San Francisco ( Site 1006)

San Francisco, California, United States

Smilow Cancer Hospital at Yale New Haven ( Site 1005)

New Haven, Connecticut, United States

Dana-Farber Cancer Institute (Boston) ( Site 1007)

Boston, Massachusetts, United States

Comprehensive Cancer Centers of Nevada ( Site 1012)

Las Vegas, Nevada, United States

Tennessee Oncology Nashville Drug Development Unit ( Site 7000)

Nashville, Tennessee, United States

START San Antonio ( Site 1004)

San Antonio, Texas, United States

Baylor Scott & White Medical Center - Temple ( Site 1009)

Temple, Texas, United States

Northwest Medical Specialties, PLLC ( Site 1001)

Tacoma, Washington, United States

Kinghorn Cancer Centre ( Site 6000)

Darlinghurst, New South Wales, Australia

Southern Oncology Clinical Research Unit SOCRU ( Site 6002)

Bedford Park, South Australia, Australia

Monash Health-Monash Medical Centre ( Site 6001)

Clayton, Victoria, Australia

Prince of Wales Hospital ( Site 2002)

Hong Kong, , Hong Kong

Queen Mary Hospital ( Site 2001)

Hong Kong, , Hong Kong

New Zealand Clinical Research (Christchurch) ( Site 6501)

Christchurch, Canterbury, New Zealand

Auckland City Hospital ( Site 6500)

Auckland, , New Zealand

National University Hospital ( Site 3006)

Singapore, Central Singapore, Singapore

National Cancer Centre Singapore ( Site 3005)

Singapore, Central Singapore, Singapore

Tan Tock Seng Hospital ( Site 3007)

Singapore, Central Singapore, Singapore

Asan Medical Center ( Site 0802)

Songpagu, Seoul, South Korea

Seoul National University Hospital ( Site 0801)

Seoul, , South Korea

Severance Hospital ( Site 0800)

Seoul, , South Korea

National Cheng Kung University Hospital ( Site 4002)

Tainan City, , Taiwan

National Taiwan University Hospital ( Site 4000)

Taipei, , Taiwan

Taipei Veterans General Hospital ( Site 4001)

Taipei, , Taiwan

Countries

United States; Australia; Hong Kong; New Zealand; Singapore; South Korea; Taiwan

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

V941-001

Identifier Type: OTHER

Identifier Source: secondary_id

V941-001

Identifier Type: -

Identifier Source: org_study_id