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

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ClinicalTrials.gov Identifier: NCT03948763
Recruitment Status : Not yet recruiting
First Posted : May 14, 2019
Last Update Posted : May 14, 2019
Sponsor:
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
Estimated Study Start Date : July 2, 2019
Estimated Primary Completion Date : June 10, 2021
Estimated Study Completion Date : March 3, 2022

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 periphery.

  3. 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

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

Inclusion Criteria:

Part 1 Only

- Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor confirmed by central laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit.

Part 2 Only

- Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), adenocarcinoma of the colon or rectum, or pancreatic adenocarcinoma, central laboratory confirmed Human Leukocyte Antigen (HLA) (HLA-A*11 and/or HLA-C*08 allele and mutated KRAS 4MUT+ (G12D, G12V, G13D or G12C) who have received, or been intolerant to or ineligible for all treatment known to confer clinical benefit)

All

  • 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 provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • 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 AEs (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 ClinicalTrials.gov identifier (NCT number): NCT03948763


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director, MD Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03948763     History of Changes
Other Study ID Numbers: V941-001
V941-001 ( Other Identifier: Merck Protocol Number )
First Posted: May 14, 2019    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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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.:
cancer
solid tumors
Pembrolizumab
PD1
PD-1
PDL1
PD-L1
KRAS
mRNA

Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Pancreatic Neoplasms
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Lung Diseases
Respiratory Tract Diseases
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents