Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors

Status: Active

Description

The purpose of this study is to assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors, and in combination with pembrolizumab in subjects with unresectable solid tumors.

Eligibility Criteria

Inclusion Criteria

  • Male or female, ≥ 18 years old with the ability to understand and provide signed and witnessed informed consent, and agree to comply with protocol requirements
  • Part A: Subjects must have one of the histologically-confirmed solid malignancies listed below, must be clinically disease-free at study entry (i.e., subjects in the adjuvant setting). Subjects will be permitted to complete any standard of care adjuvant therapy prior to study entry, and those not eligible for any standard of care adjuvant treatment, or who decline such treatment, are permitted to consent to this study, as long as all treatment options have been transparently disclosed and documented in the Subject's medical record
  • Part B: Subjects must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, AND have measurable disease at study entry defined by RECIST 1.1. AND be considered suitable for treatment with pembrolizumab; in this study pembrolizumab will be considered an investigational study drug. Subjects with any of the following solid malignancies: a. Non-small cell lung cancer (subjects in Part B must either lack EGFR sensitizing mutation or ALK translocation per local test results, or must have progressed on approved standard of care treatment for EGFR or ALK positive NSCLC) b. Small cell lung cancer c. Melanoma d. Bladder urothelial carcinoma e. Human papillomavirus-negative HNSCC f. Any solid malignancy known to be MSI high/MMR deficient per local test results, including but not limited to: CRC, stomach adenocarcinoma, esophageal adenocarcinoma and endometrial cancer
  • Part C: Subjects must have one of the histologically‑ or cytologically confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, AND must not have received prior anti‑PD‑1/PD-L1 therapy, AND must have measurable disease at study entry defined by RECIST 1.1
  • MSS-CRC
  • HPV negative metastatic or recurrent HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx
  • Bladder urothelial carcinoma
  • Part D: Subject must have completed resected adjuvant melanoma and must be clinically disease-free at study entry (i.e., subjects in the adjuvant setting). Subjects will be permitted to complete any standard of care adjuvant therapy prior to study entry, and those not eligible for any standard of care adjuvant treatment, or who decline such treatment, are permitted to consent to this study, as long as all treatment options have been transparently disclosed and documented in the subject's medical record
  • Parts A and D: subjects must have a FFPE tumor sample available (e.g., from their prior surgery) that is suitable for the next generation sequencing (NGS) required for this study.
  • Parts B and C: subjects must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry and provide a biopsy suitable for the NGS required for this study. An existing (archival) FFPE tumor sample may instead be used for NGS after discussing with medical monitor
  • Subjects must have resolution of toxic effect(s) from prior therapy to Grade 1 or less. Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion. If a subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention to Grade 1 or less
  • Subject is willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug (male and female participants of childbearing potential)
  • Subjects with PS of 0 or 1 on the ECOG Performance Scale
  • Life expectancy > 12 weeks at Screening
  • Subjects with adequate organ and marrow function
  • Parts A and D: Subject must consent to required apheresis procedure and meet additional inclusion criteria per local institutional apheresis procedure

Exclusion Criteria

  • Treatment with any of the following:
  • Any investigational agents, anti-cancer monoclonal antibody, anti-cancer therapeutic vaccine, immunostimulant (e.g. IL-2) or study drugs from a previous clinical study within 4 weeks of the first dose of mRNA-4157 or pembrolizumab (note only a 2 week wash out is required from prior pembrolizumab treatment)
  • Any chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first dose of mRNA-4157 or pembrolizumab
  • Live-virus vaccination within 30 days of the first dose of mRNA-4157 or pembrolizumab. Seasonal flu vaccines that do not contain live virus are permitted
  • Any systemic steroid therapy or other form of immunosuppressive therapy within 7 days of the first dose of mRNA-4157 or pembrolizumab
  • Transfusion of blood products (including platelets or red blood cells[RBCs]) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 1 week of the NGS blood sample during screening, and 4 weeks of the first dose of mRNA-4157 or pembrolizumab
  • Prior PD-1/PD-L1 treatment is permitted for subjects in Parts A, B and D of this study, but only subjects who have progressed on their prior PD-1/PD-L1 treatment without a partial or complete response, and without discontinuing for drug-related toxicity are eligible
  • Active central nervous system metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
  • Has a diagnosis of immunodeficiency
  • Any clinically-significant cardiac disease defined as New York Heart Association class III or IV within the past 6 months of Screening, unless, in the opinion of the Investigator, the disease is well-controlled
  • A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Previously identified hypersensitivity to components of the formulations used in this study
  • Had a solid organ or allogeneic bone marrow transplant
  • Subjects with a history of interstitial lung disease
  • An active infection requiring systemic therapy
  • A known history of HIV
  • Known active Hepatitis B or Hepatitis C
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone curative therapy or in situ cervical cancer
  • Subjects participating in apheresis; mandatory in the Part A apheresis expansion phase cohort and Part D (optional for other study parts), must not meet any of the exclusion criteria on any day when apheresis is performed, either protocol specific apheresis criteria, or per local institutional apheresis protocol.

Locations & Contacts

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Name Not Available

North Carolina

Durham
Duke University Medical Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Moderna Therapeutics

Trial IDs

Primary ID mRNA-4157-P101
Secondary IDs NCI-2018-00215
Clinicaltrials.gov ID NCT03313778