Clinical Trials /

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

NCT03948763

Description:

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.

Related Conditions:
  • Colorectal Neoplasm
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: V941-001
  • SECONDARY ID: V941-001
  • NCT ID: NCT03948763

Conditions

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

Interventions

DrugSynonymsArms
V941mRNA-5671/V941V941 Monotherapy
PembrolizumabV941 + Pembrolizumab

Purpose

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 Arms

NameTypeDescriptionInterventions
V941 MonotherapyExperimentalV941(mRNA-5671/V941) administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles
  • V941
V941 + PembrolizumabExperimentalV941(mRNA-5671/V941) administered IM Q3W for 9 cycles and pembrolizumab 200 mg, intravenous (IV) for 35 3-week cycles
  • V941
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        Part 2 Only

        - Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC),
        non-microsatellite instability-high colorectal neoplasms (non-MSI-H CRC) or pancreatic
        adenocarcinoma, and centrally confirmed Human Leukocyte Antigen (HLA) HLA-A*1101 and/or
        HLA-C*0802 allele expression by HLA typing

        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
             central 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Limiting Toxicities (DLTs)
Time Frame:Cycle 1 (Up to 21 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description: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).
Measure:Mutant KRAS Specific T cells
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Presence of and changes in the quantity of mutant KRAS specific T cells in the periphery.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

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

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