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

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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: Participants must have one of the histologically-confirmed solid malignancies listed below, must be clinically disease-free at study entry (that is, participants in the adjuvant setting).
Participants 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 participant's medical record.
  • - Part B: Participants must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, have measurable disease at study entry defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
, and be considered suitable for treatment with pembrolizumab; in this study pembrolizumab will be considered an investigational study drug. Participants with any of the following solid malignancies: a. Non-small cell lung cancer (participants in Part B must either lack epidermal growth factor receptor (EGFR) sensitizing mutation or anaplastic lymphoma kinase (ALK) translocation per local test results or must have progressed on approved standard of care treatment for EGFR or ALK positive non-small cell lung cancer [NSCLC]) b. Small cell lung cancer c. Melanoma d. Bladder urothelial carcinoma e. Human papillomavirus-negative head and neck squamous cell carcinoma (HPV-ve HNSCC) f. Any solid malignancy known to be microsatellite instable (MSI) high/mismatch repair (MMR) deficient g. Any solid malignancy known to have a high tumor mutational load/burden.
  • - Part C: Participants must have one of the histologically- or cytologically confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, must not have received prior anti-programmed cell death protein 1 (PD-1)/programmed death -ligand 1 (PD-L1) therapy, and must have measurable disease at study entry defined by RECIST 1.1.
1. Microsatellite stable (MSS)-CRC. 2. HPV-ve metastatic or recurrent HPV-ve HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx. 3. Bladder urothelial carcinoma.
  • - Part D: Participants must have completed resected adjuvant melanoma and must be clinically disease-free at study entry.
Participants 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 participant's medical record.
  • - Parts A and D: Participants must have a formalin-fixed paraffin embedded (FFPE) tumor sample available (for example, from their prior surgery) that is suitable for the next generation sequencing (NGS) required for this study.
  • - Parts B and C: Participants must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry and provide a biopsy suitable for the next generation sequencing (NGS) required for this study.
An existing (archival) FFPE tumor sample may instead be used for NGS after discussing with medical monitor.
  • - Participants must have resolution of toxic effect(s) from prior therapy to Grade 1 or less.
Participants with Grade ≤2 neuropathy or alopecia are an exception to this criterion. If a participant received major surgery or radiation therapy of >30 gray (Gy), they must have recovered from the toxicity and/or complications from the intervention to Grade 1 or less.
  • - Participant 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).
  • - Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS.
  • - Life expectancy >12 weeks at Screening.
  • - Participants with adequate organ and marrow function.
  • - Parts A and D: Participant must consent to required apheresis procedure and meet additional inclusion criteria per local institutional apheresis procedure.

Exclusion Criteria:

  • - Treatment with any of the following: 1.
Any investigational agents, anti-cancer monoclonal antibody, anti-cancer therapeutic vaccine, immunostimulant (for example, 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) 2. Any chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first dose of mRNA-4157 or pembrolizumab. 3. 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. 4. Any systemic steroid therapy or other form of immunosuppressive therapy within 7 days of the first dose of mRNA-4157 or pembrolizumab. 5. Transfusion of blood products (including platelets or red blood cells [RBCs]) or administration of colony stimulating factors (including granulocyte colony stimulating factor [G-CSF], granulocyte/macrophage colony stimulating factor [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 participants in Parts A, B, and D of this study, but only participants 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 participation for the full duration of the study, or is not in the best interest of the participant 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.
  • - Participants with a history of interstitial lung disease.
  • - An active infection requiring systemic therapy.
  • - A known history of human immunodeficiency virus (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.
  • - Participants 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03313778
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

ModernaTX, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

IndustryIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Solid Tumors
Additional Details

This is a multi-part, dose-escalation study of mRNA-4157 monotherapy in participants with resected solid tumors (Part A) and of mRNA-4157 in combination with pembrolizumab in participants with both unresectable (locally advanced or metastatic) solid tumors (Parts B and C) and resected cutaneous melanoma (Part D). Parts A and B will include a dose escalation phase of the study to identify doses of mRNA-4157 for the expansion phase of the study. Doses of mRNA-4157 will be administered to participants in a dose escalation regimen. Participants in Parts B, C, and D dose expansion phase will receive mRNA-4157 at a recommended dose for expansion.

Arms & Interventions

Arms

Experimental: Part A: Dose Escalation

Participants will receive a fixed applicable dose of mRNA-4157 administered via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles.

Experimental: Part B: Dose Escalation

Participants will receive a fixed applicable dose of mRNA-4157 administered via an IM injection on Day 1 of each 21-day cycle for up to 9 cycles and fixed-dose of pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.

Experimental: Part A: Dose Expansion

Participants will receive mRNA-4157 via IM injection at an applicable dose, identified during the dose escalation phase of the study, on Day 1 of each 21-day cycle for up to 9 cycles.

Experimental: Part B, C, and D: Dose Expansion

Participants will receive mRNA-4157 via IM injection at an applicable dose, identified during the dose escalation phase of the study, on Day 1 of each 21-day cycle for up to 9 cycles. Participants will also receive a fixed-dose of pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.

Interventions

Biological: - mRNA-4157

Personalized cancer vaccine, IM injection

Biological: - Pembrolizumab

Intravenous infusion

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you. Please note all sites listed may not currently be active in the trial. Please continue to check back for additional site locations.

University of Arizona, Tucson, Arizona

Status

Recruiting

Address

University of Arizona

Tucson, Arizona, 85721

Florida Cancer Specialists, Sarasota, Florida

Status

Recruiting

Address

Florida Cancer Specialists

Sarasota, Florida, 34232

Massachusetts General Hospital, Boston, Massachusetts

Status

Recruiting

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

John Theurer Cancer Center, Hackensack, New Jersey

Status

Recruiting

Address

John Theurer Cancer Center

Hackensack, New Jersey, 07601

NYU Langone, New York, New York

Status

Recruiting

Address

NYU Langone

New York, New York, 10016

Duke Cancer Institute, Durham, North Carolina

Status

Recruiting

Address

Duke Cancer Institute

Durham, North Carolina, 27710

Nashville, Tennessee

Status

Recruiting

Address

Sarah Cannon Research Institute, Tennessee Oncology

Nashville, Tennessee, 37203