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Solid TumorsPhase 1KEYNOTE-603NCT03313778

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

A Phase 1 study testing mRNA-4157, Pembrolizumab and SoC Treatment in people with Solid Tumors, run by ModernaTX, Inc. at 20 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
mRNA-4157, Pembrolizumab and SoC Treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
161 participants
Where
20 sitesin 4 countries
Study dates
14 Aug 2017to 21 Nov 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.
  • Note: Additional inclusion/exclusion criteria may apply, per protocol.

Trial locations and contacts

20 sites in 4 countries.

20 sites in 4 countries

United States10 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195-0001

  • UT Southwest Medical Center

    Dallas, Texas, 75390

  • Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • NYU Langone Medical Center

    New York, New York, 10016

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15219

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612-9416

  • The George Washington Cancer Center

    Washington D.C., District of Columbia, 20037

Other trials in United States

Japan4 sites

  • National Cancer Center Hospital

    Chuo-Ku, Tokyo, 104-0045

  • National Cancer Center East

    Kashiwa-Shi, Chiba, 277-8577

  • Kindai University Hospital

    Osakasayama-Shi, Ôsaka, 589-0014

  • The Cancer Institute Hospital of Japanese Foundation For Cancer Research

    Tokyo, 135-8550

Other trials in Japan

Australia3 sites

  • St Vincents Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • One Clinical Research Perth

    Nedlands, Western Australia, 6009

  • Westmead Hospital-Cnr Hawkesbury and Darcy Road

    Westmead, New South Wales, 2145

Other trials in Australia

United Kingdom3 sites

  • Ninewells Hospital - PPDS

    Dundee, Scotland, DD1 9SY

  • Imperial College Healthcare NHS Trust Hammersmith Hospital

    London, W12 0HS

  • Royal Mardsen Sutton

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors

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.

Read the detailed description

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
Solid Tumors
Being tested
mRNA-4157, Pembrolizumab, SoC Treatment
Keywords
mRNA-4157, PCV, pembrolizumab, Moderna, intismeran autogene

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mRNA-4157Biological

    IM injection

  • PembrolizumabBiological

    Intravenous infusion

  • SoC TreatmentBiological

    Also called Standard of care chemotherapy

    Intravenous infusion

Study groups in NCT03313778
Study groupRoleWhat they receive
Part A: Dose Escalation and Dose ExpansionExperimentalParticipants will receive mRNA-4157 via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles.
Receives: Biological: mRNA-4157
Part B: Dose Escalation and Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab
Part A2: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: SoC Treatment
Part C: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab
Part D: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab
Part E1: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment
Part E2: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment
Part E3: Dose ExpansionExperimentalParticipants 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.
Receives: Biological: mRNA-4157; Biological: Pembrolizumab; Biological: SoC Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Adverse Events

    Measured: 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)

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

    ORR is defined as the proportion of participants whose best overall response is complete response (CR) or partial response (PR).

    Measured: 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)

  2. Part C: Duration of Response (DoR)

    DoR is defined as time from first tumor response (partial or complete) until either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner).

    Measured: 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)

  3. Part C: Progression Free Survival (PFS)

    PFS is defined as time between the date of first dose of pembrolizumab and the date of either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner).

    Measured: 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)

  4. Part C: Overall Survival (OS)

    OS is defined as time between the date of the first dose of study drug and the date of death due to any cause.

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

  5. Part A2: Recurrence-free Survival (RFS)

    RFS is defined as the time between the date of first dose of mRNA-4157 and the date of one of the following events: radiological disease relapse, clinical/symptomatic disease progression as assessed by the investigator or death due to any cause.

    Measured: Baseline up to 2 years

  6. Parts A2, E1, E2, and E3: Number of Participants with Presence or Absence of Circulating Tumor DNA (ctDNA)

    Presence or absence of ctDNA prior to start of treatment as well as across longitudinal study timepoints, and association with RFS.

    Measured: Baseline up to 2 years

  7. Parts E1 and E2: Event-free Survival (EFS)

    EFS is defined as the time from date of the first dose of study drug to the first of the following events: radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local, regional, or distant recurrence, or death due to any cause and will be determined either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    Measured: Baseline up to 2 years

  8. Part E3: EFS

    EFS, based on RECIST 1.1, is defined as the time from date of the first dose of study drug to the first of the following events: radiographic disease progression per RECIST 1.1; local, regional or distant recurrence as assessed by computed tomography scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause.

    Measured: Baseline up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2017
  2. Study start14 Aug 2017
  3. Primary completion21 Nov 2027 (estimated)
  4. Study completion21 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
161 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03313778
Sponsor's protocol ID
mRNA-4157-P101
Other IDs
2023-505192-77-00, 2023
Acronym
KEYNOTE-603
Status last verified
Aug 2026
First submitted
13 Oct 2017
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39485256

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing mRNA-4157, Pembrolizumab and SoC Treatment in people with Solid Tumors, run by ModernaTX, Inc. at 20 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Japan, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Adverse Events (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03313778, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.

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