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

NCT03948763 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: V941-001
• Study Type: interventional
• Target: 70
• Locations: 7 countries
• Sites: 26

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

Keywords

cancer; solid tumors; therapeutic vaccine; Pembrolizumab; PD1; PD-1; PDL1; PD-L1; KRAS; mRNA

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicities (DLTs)

  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.

  Cycle 1 (Up to 21 days)

• Number of Participants Who Experienced an Adverse Event (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.

  Up to approximately 27 months

• Number of Participants Who Discontinued Study Treatment 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. The number of participants who discontinued study treatment due to an AE is reported.

  Up to approximately 24 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to approximately 24 months

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

  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)

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

  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)

Other Outcomes (1)

• T-cell Receptor (TCR) Clonality and Diversity

  Up to approximately 24 months

Study Arms (5)

Part 1: V941 Monotherapy

EXPERIMENTAL

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

Biological: V941

Part 1: V941 + Pembrolizumab

EXPERIMENTAL

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

Biological: V941; Biological: Pembrolizumab

Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab)

EXPERIMENTAL

V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles

Biological: V941; Biological: Pembrolizumab

Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab)

EXPERIMENTAL

V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles

Biological: V941; Biological: Pembrolizumab

Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab)

EXPERIMENTAL

V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles

Biological: V941; Biological: Pembrolizumab

Interventions

V941 BIOLOGICAL

V941 administered IM, Q3W for 9 3-week cycles

Also known as: mRNA-5671/V941

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)

Pembrolizumab BIOLOGICAL

Pembrolizumab 200 mg, IV for 35 3-week cycles

Also known as: MK-3475

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• ModernaTX, Inc.: collaborator

Study Sites (26)

Banner MD Anderson Cancer Center ( Site 1008)

Gilbert, Arizona, 85234, United States

Location

City of Hope ( Site 1002)

Duarte, California, 91010, United States

Location

University of California at San Francisco ( Site 1006)

San Francisco, California, 30322, United States

Location

Smilow Cancer Hospital at Yale New Haven ( Site 1005)

New Haven, Connecticut, 06510, United States

Location

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

Boston, Massachusetts, 02215, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 1012)

Las Vegas, Nevada, 89169, United States

Location

Tennessee Oncology Nashville Drug Development Unit ( Site 7000)

Nashville, Tennessee, 37203, United States

Location

START San Antonio ( Site 1004)

San Antonio, Texas, 78229, United States

Location

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

Temple, Texas, 76508, United States

Location

Northwest Medical Specialties, PLLC ( Site 1001)

Tacoma, Washington, 98405, United States

Location

Kinghorn Cancer Centre ( Site 6000)

Darlinghurst, New South Wales, 2010, Australia

Location

Southern Oncology Clinical Research Unit SOCRU ( Site 6002)

Bedford Park, South Australia, 5042, Australia

Location

Monash Health-Monash Medical Centre ( Site 6001)

Clayton, Victoria, 3168, Australia

Location

Prince of Wales Hospital ( Site 2002)

Hong Kong, Hong Kong

Location

Queen Mary Hospital ( Site 2001)

Hong Kong, Hong Kong

Location

New Zealand Clinical Research (Christchurch) ( Site 6501)

Christchurch, Canterbury, 8011, New Zealand

Location

Auckland City Hospital ( Site 6500)

Auckland, 1023, New Zealand

Location

National University Hospital ( Site 3006)

Singapore, Central Singapore, 119074, Singapore

Location

National Cancer Centre Singapore ( Site 3005)

Singapore, Central Singapore, 169610, Singapore

Location

Tan Tock Seng Hospital ( Site 3007)

Singapore, Central Singapore, 398442, Singapore

Location

Asan Medical Center ( Site 0802)

Songpagu, Seoul, 05505, South Korea

Location

Seoul National University Hospital ( Site 0801)

Seoul, 03080, South Korea

Location

Severance Hospital ( Site 0800)

Seoul, 03722, South Korea

Location

National Cheng Kung University Hospital ( Site 4002)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 4000)

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital ( Site 4001)

Taipei, 11217, Taiwan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

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

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp and Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2019
• First Posted: May 14, 2019
• Study Start: June 26, 2019
• Primary Completion: August 25, 2022
• Study Completion: August 25, 2022
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

TW (3); AU (3); SG (3); US (10); HK (2); NZ (2); KR (3)