Treatment

Moderna’s Personalized mRNA Cancer Vaccine Programs in NSCLC

By September 3, 2026No Comments

mRNA cancer vaccines are showing early promise — here’s what’s known so far, and what RET-positive patients should ask their care team.

We have been following the exciting progress in personalized mRNA cancer vaccines, particularly the encouraging results recently reported by Moderna and Merck in melanoma. While these results are in a different cancer type and do not yet demonstrate that the approach will be effective in NSCLC, they represent an important development for the broader field of personalized cancer immunotherapy.

Key Takeaways

Moderna mRNA vaccines are personalized to your tumor. Unlike a regular vaccine, these are custom-made using the specific mutations found in your own cancer, to help your immune system recognize and attack it.
Recent results are promising — but they're for melanoma, not lung cancer yet. Moderna and Merck's vaccine (V940) showed positive results in melanoma cancer patients. That's encouraging for the science, but it doesn't yet prove the vaccine works for NSCLC.
You currently can't combine this vaccine with a RET-targeted pill. Because RET is an actionable alteration and the tumor driver, effective RET-targeted therapies are considered the preferred first-line treatment option, and at this time, these studies do not permit patients to receive the investigational therapies in combination with a RET-targeted pilI.
A lung cancer trial is underway, but RET eligibility is unclear. The INTerpath-002 trial tests personalized V940 vaccine + pembrolizumab after complete resection of stage II–IIIB NSCLC (early stage). The trial excludes tumors with sensitizing EGFR and ALK mutations, but the publicly available criteria do not clearly state that RET-positive tumors are excluded.
mRNA-4359: A Vaccine That Targets How Cancer Hides From Your Immune System. It helps your immune system find and fight cancer cells that are hiding from it. One part of the trial has closed, but another part is open to patients whose immunotherapy has stopped working — RET-positive patients can join, but only after trying the RET-targeted pill first (or discussing it with their doctor).

Because some of these approaches are also being studied in NSCLC, we wanted to take a closer look at Moderna’s ongoing programs and what is currently known about their potential relevance to people living with NSCLC.

Moderna is investigating several mRNA-based approaches to cancer, including V940 (mRNA-4157), a personalized neoantigen therapy, and mRNA-4359, an immune-evasion-targeted cancer antigen therapy.

V940 (mRNA-4157): A Personalized Cancer Vaccine

V940 (mRNA-4157), also known as intismeran autogene, is an investigational individualized mRNA-based neoantigen therapy. Each treatment is personalized to the patient and contains synthetic mRNA encoding up to 34 neoantigens selected based on the unique mutational profile of the patient’s tumor. The goal is to stimulate the immune system to recognize and attack cancer cells.

Results in Melanoma

INTerpath-001 (NCT05933577) is a global Phase 3 trial evaluating V940 in combination with pembrolizumab, compared with pembrolizumab alone, in patients with completely resected high-risk stage IIB-IV cutaneous melanoma. In August 2026, Merck and Moderna announced positive topline results from the trial, supporting the potential of this personalized mRNA approach in the adjuvant treatment of melanoma.

INTerpath-002: V940 in Resected NSCLC

INTerpath-002 (NCT06077760) is a Phase 3 trial evaluating V940 in combination with pembrolizumab in patients with completely resected stage II, IIIA, or IIIB NSCLC. The trial is evaluating whether this personalized vaccine approach can improve outcomes in the adjuvant setting. A 2026 report stated that patients with EGFR or ALK alterations are not eligible for the trial. The available information does not clarify whether RET-positive patients are excluded. Patients should confirm eligibility directly with the study team.

KEYNOTE-603

KEYNOTE-603 (NCT03313778) evaluated the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination with pembrolizumab in patients with advanced or metastatic solid tumors, including NSCLC. Earlier research demonstrated the generation of de novo and enhancement of existing neoantigen-specific T-cell responses. The study is not currently recruiting.

mRNA-4359: Targeting Cancer Immune Evasion

mRNA-4359 is an investigational cancer antigen therapy targeting immune evasion. It encodes epitopes from PD-L1 and IDO1, proteins involved in mechanisms that can help cancer cells evade the immune system. It is being evaluated both alone and in combination with pembrolizumab.

MOBILIZE Trial

The MOBILIZE trial (NCT05533697) is a Phase 1/2 study evaluating mRNA-4359 in adults with selected advanced solid tumors.

Arm 1a: Metastatic NSCLC 

Arm 1a evaluated mRNA-4359 in patients with metastatic NSCLC who had progressed, relapsed, or become intolerant to-or were ineligible for-at least one standard treatment regimen.

Important: As of January 2025, Moderna confirmed that Arm 1a is closed, with no further enrollment opportunities.

Arm 1b: Immune Checkpoint Inhibitor (CPI)-Refractory NSCLC

Arm 1b is evaluating mRNA-4359 in patients with locally advanced or metastatic, CPI-refractory NSCLC or melanoma. The trial specifies that patients with EGFR, ALK, ROS1, or other actionable mutations for which approved targeted therapies are available must have received the appropriate targeted therapy or have been offered and declined it.

Important: Because RET is an actionable alteration with approved and effective RET-targeted therapies that are generally considered the preferred first-line treatment option, patients should carefully discuss their individual treatment history, current disease status, and potential eligibility with their care team before considering enrollment. At this time, these studies do not allow patients to receive the investigational therapies in combination with a RET TKI.

Additional Resources

See more information on NSCLC vaccines

BioNTech’s BNT116 mRNA cancer vaccine trial currently open at MD Anderson and Johns Hopkins

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