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

NCT ID: NCT03313778

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

242 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-14

Study Completion Date

2027-08-01

Brief Summary

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

Detailed Description

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This is a multi-part, dose-escalation study of mRNA-4157 monotherapy in participants with resected solid tumors (Part A), mRNA-4157 monotherapy lead-in and then in combination with standard of care (SoC) adjuvant chemotherapy followed by mRNA-4157 monotherapy in participants with resected pancreatic ductal adenocarcinoma (PDAC) (Part A2), mRNA-4157 in combination with pembrolizumab in participants with both unresectable (locally advanced or metastatic) solid tumors (Parts B and C) and adjuvant resected cutaneous melanoma (Part D), and mRNA-4157 in combination with pembrolizumab and SoC chemotherapy in peri-operative setting in participants with non-squamous non-small cell lung cancer (NSCLC) (Part E1), squamous cell NSCLC (Part E2), and gastric/ gastroesophageal (GEJ) cancer (Part E3). 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 A2, B, C, D, E1, E2 and E3 dose expansion phase will receive mRNA-4157 at a recommended dose for expansion.

Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: Dose Escalation and Dose Expansion

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

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Part B: Dose Escalation and Dose Expansion

Participants will receive mRNA-4157 via an IM injection on Day 1 of each 21-day cycle for up to 9 cycles and 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.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

Part A2: Dose Expansion

Participants will receive mRNA-4157 via an IM injection on Day 1 of each 21-day cycle and a SoC treatment every 2 weeks (Q2W) on Day 1 of each 21-day cycle starting from Cycle 5 of mRNA-4157 for up to 12 cycles.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

SoC Treatment

Intervention Type BIOLOGICAL

Intravenous infusion

Part C: Dose Expansion

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle for up to 9 cycles and 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.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

Part D: Dose Expansion

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle for up to 9 cycles and pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 18 cycles (approximately 1 year of treatment), whichever is sooner.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

Part E1: Dose Expansion

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab every 6 weeks (Q6W) via IV infusion, and SoC chemotherapy every 3 weeks (Q3W) for up to 4 cycles during the perioperative and adjuvant phases.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

SoC Treatment

Intervention Type BIOLOGICAL

Intravenous infusion

Part E2: Dose Expansion

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab Q6W via IV infusion, and SoC chemotherapy Q3W for up to 4 cycles during the perioperative and adjuvant phases.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

SoC Treatment

Intervention Type BIOLOGICAL

Intravenous infusion

Part E3: Dose Expansion

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab Q3W via IV infusion, and SoC chemotherapy Q2W or Q3W for up to 4 cycles during the perioperative and adjuvant phases.

Group Type EXPERIMENTAL

mRNA-4157

Intervention Type BIOLOGICAL

IM injection

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion

SoC Treatment

Intervention Type BIOLOGICAL

Intravenous infusion

Interventions

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mRNA-4157

IM injection

Intervention Type BIOLOGICAL

Pembrolizumab

Intravenous infusion

Intervention Type BIOLOGICAL

SoC Treatment

Intravenous infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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Standard of care chemotherapy

Eligibility Criteria

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Inclusion Criteria

* Parts A, A2, and D: Participants must be clinically disease-free at study entry (that is, participants in the adjuvant setting).
* Part B: Participants must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) protocol-specified solid malignancies, 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.
* Part C: Participants must have one of the histologically- or cytologically confirmed unresectable (locally advanced or metastatic) protocol-specified solid malignancies, 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.
* Part A2: Participants with histologically confirmed PDAC who have undergone complete macroscopic resection(that is, R0 - no cancer cells within 1 mm of all resection margins or R1 - cancer cells present within 1 mm of one or more resection margins) who had no evidence of metastatic disease with adequate recovery from surgery to receive adjuvant therapy.
* Parts E1 and E2: Participants with untreated histologically/cytologically confirmed Stage II-IIIB NSCLC (per AJCC version 8) that is considered resectable of non-squamous (adenocarcinoma only) or squamous cell carcinoma histology, absence of major associated pathologies that increase the surgery risk to an unacceptable level, must have a tumor tissue sample available for NGS and PD-L1 IHC testing as defined in the Laboratory Manual.
* Part E3: Participants with untreated, locally advanced surgically resectable, histologically/cytologically confirmed, gastric/GEJ adenocarcinoma, as defined by a primary lesion that is T3 or greater or with the presence of any positive clinical nodes (N+) and without evidence of metastatic disease, measurable disease according to RECIST version 1.1, absence of major associated pathologies that increase the surgery risk to an unacceptable level, must have a tumor tissue sample available for NGS and PD-L1 IHC testing as defined in the Laboratory Manual.
* Part D: Participants with completely resected Stage II, III or IV cutaneous melanoma.
* Parts A, A2, 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.
* Participants must have resolution of toxic effect(s) (as specified in the protocol) from prior therapy 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), or for a specified time after the last dose of SoC chemotherapy per SoC product labeling, whichever is later.
* Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS.

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
* 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 chemotherapy agents that the participant would receive in their specific cohort or to components of the formulations used in this study
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

ModernaTX, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The George Washington Cancer Center

Washington D.C., District of Columbia, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Westmead Hospital-Cnr Hawkesbury and Darcy Road

Westmead, New South Wales, Australia

Site Status

One Clinical Research Perth

Perth, Western Australia, Australia

Site Status

National Cancer Center East

Chiba, , Japan

Site Status

Kindai University Hospital

Osaka, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, , Japan

Site Status

NHS Tayside

Dundee, Scotland, United Kingdom

Site Status

Royal Mardsen London

London, , United Kingdom

Site Status

Royal Mardsen Sutton

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Japan United Kingdom

References

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Berraondo P, Cuesta R, Sanmamed MF, Melero I. Immunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines. Cancer Discov. 2024 Nov 1;14(11):2021-2024. doi: 10.1158/2159-8290.CD-24-1196.

Reference Type DERIVED
PMID: 39485256 (View on PubMed)

Other Identifiers

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2023-505192-77-00

Identifier Type: OTHER

Identifier Source: secondary_id

mRNA-4157-P101

Identifier Type: -

Identifier Source: org_study_id

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