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

NCT03313778 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: mRNA-4157-P1012023-505192-77-00
• Study Type: interventional
• Target: 161
• Locations: 4 countries
• Sites: 20

Brief Summary

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.

Conditions

Solid Tumors

Keywords

mRNA-4157; PCV; pembrolizumab; Moderna; intismeran autogene

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events

  Part A and A2: Baseline through 100 days after last mRNA-4157 dose; Parts B, C, D, E1, E2, and E3: Baseline through 90 days after last pembrolizumab dose

Secondary Outcomes (8)

• Part C: Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete)

  Baseline through disease progression by Response Evaluation Criteria of Solid Tumors Version 1.1 (RECIST 1.1), start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Part C: Duration of Response (DoR)

  Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Part C: Progression Free Survival (PFS)

  Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Part C: Overall Survival (OS)

  Baseline to death of any cause (up to approximately 3 years)

• Part A2: Recurrence-free Survival (RFS)

  Baseline up to 2 years

Study Arms (8)

Part A: Dose Escalation and Dose Expansion

EXPERIMENTAL

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

Biological: mRNA-4157

Part B: Dose Escalation and Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab

Part A2: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: SoC Treatment

Part C: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab

Part D: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab

Part E1: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment

Part E2: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment

Part E3: Dose Expansion

EXPERIMENTAL

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.

Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment

Interventions

mRNA-4157 BIOLOGICAL

IM injection

Part A2: Dose Expansion; Part A: Dose Escalation and Dose Expansion; Part B: Dose Escalation and Dose Expansion; Part C: Dose Expansion; Part D: Dose Expansion; Part E1: Dose Expansion; Part E2: Dose Expansion; Part E3: Dose Expansion

Pembrolizumab BIOLOGICAL

Intravenous infusion

Part B: Dose Escalation and Dose Expansion; Part C: Dose Expansion; Part D: Dose Expansion; Part E1: Dose Expansion; Part E2: Dose Expansion; Part E3: Dose Expansion

SoC Treatment BIOLOGICAL

Intravenous infusion

Also known as: Standard of care chemotherapy

Part A2: Dose Expansion; Part E1: Dose Expansion; Part E2: Dose Expansion; Part E3: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Treatment with any of the following:
• 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)
• 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 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (20)

Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

The George Washington Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9416, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195-0001, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15219, United States

Location

UT Southwest Medical Center

Dallas, Texas, 75390, United States

Location

St Vincents Hospital Sydney

Darlinghurst, New South Wales, Australia

Location

Westmead Hospital-Cnr Hawkesbury and Darcy Road

Westmead, New South Wales, 2145, Australia

Location

One Clinical Research Perth

Nedlands, Western Australia, 6009, Australia

Location

National Cancer Center East

Kashiwa-Shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, 135-8550, Japan

Location

Kindai University Hospital

Osakasayama-Shi, Ôsaka, 589-0014, Japan

Location

Ninewells Hospital - PPDS

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Royal Mardsen Sutton

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Imperial College Healthcare NHS Trust Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39485256 DERIVED

MeSH Terms

Interventions

pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 18, 2017
• Study Start: August 14, 2017
• Primary Completion (Estimated): November 21, 2027
• Study Completion (Estimated): November 21, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); JP (4); US (10); AU (3)