Related Experiment Video

Updated: May 26, 2026

A Melanoma Patient-Derived Xenograft Model
07:07

A Melanoma Patient-Derived Xenograft Model

Published on: May 20, 2019

12.4K

Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected

Jeffrey S Weber1, Matteo S Carlino2, Adnan Khattak3

  • 1Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, New York, NY, USA.

Lancet (London, England)
|January 21, 2024
PubMed
Abstract

Insights

Adjuvant mRNA-4157 (V940) combined with pembrolizumab improved recurrence-free survival in high-risk melanoma patients compared to pembrolizumab alone. This novel mRNA neoantigen therapy demonstrated a manageable safety profile in the adjuvant setting.

Area of Science:

  • Oncology
  • Immunotherapy
  • Melanoma Research

Background:

  • Checkpoint inhibitors are standard adjuvant treatment for resected melanoma stages IIB-IV.
  • A significant number of patients treated with checkpoint inhibitors experience recurrence.
  • There is a need for more effective adjuvant therapies to improve outcomes in high-risk melanoma.

Purpose of the Study:

  • To evaluate the efficacy of mRNA-4157 (V940), an individualized neoantigen therapy, in combination with pembrolizumab.
  • To compare recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) of the combination therapy versus pembrolizumab monotherapy.
  • To assess the safety and tolerability of the combination therapy in patients with resected high-risk melanoma.

Main Methods:

  • An open-label, randomized, phase 2b adjuvant study was conducted.
  • 157 patients with completely resected high-risk cutaneous melanoma (stage IIIB-IV) were enrolled.
  • Patients were assigned 2:1 to receive mRNA-4157 plus pembrolizumab or pembrolizumab monotherapy, with mRNA-4157 administered intramuscularly and pembrolizumab intravenously every 3 weeks.

Main Results:

  • The combination therapy showed a trend towards improved RFS compared to monotherapy (HR 0.561, p=0.053).
  • 18-month RFS was 79% for the combination group versus 62% for the monotherapy group.
  • Treatment-related adverse events were predominantly grade 1-2, with a manageable safety profile and similar immune-mediated event frequencies between groups.

Conclusions:

  • Adjuvant mRNA-4157 combined with pembrolizumab prolonged recurrence-free survival in patients with resected high-risk melanoma.
  • The combination therapy demonstrated a manageable safety profile.
  • These findings suggest that individualized neoantigen mRNA therapy may offer a beneficial approach in the adjuvant treatment of melanoma.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.3K
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients07:42

Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients

Published on: February 7, 2021

4.9K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.