Cancer Vaccine for NSCLC and Melanoma Could Be Paradigm-Changing

The phase 1 study evaluating this cancer vaccine is expected to be completed in June 2025.

Some patients with skin and lung cancer continued to experience immune responses for 30 weeks after treatment with the cancer vaccine mRNA-4157, according to new study results.

Findings from the phase 1 KEYNOTE-603 study, published in Cancer Discovery, showed that among patients treated with mRNA-4157 and the immune checkpoint inhibitor Keytruda (pembrolizumab) — four with resected (surgically removed) non-small cell lung cancer and 12 with resected cutaneous melanoma — provide insight into the ability of neoantigen therapies such as mRNA-4157 to produce anti-tumor responses, as one researcher told CURE®.

“This could lead to a new treatment paradigm for patients with NSCLC and melanoma,” said corresponding author Dr. Justin Gainor, program director of the Center for Thoracic Cancers at Massachusetts General Hospital, via email.

mRNA-4157, researchers reported, is capable of targeting up to 34 patient-specific tumor neoantigens, which are genetically altered proteins present in the tumor. And, among three patients who had blood samples collected at 30 weeks or later following treatment, all had detectable anti-tumor immune responses, “which is really encouraging,” Gainor said.

In the study, the patients with non-small cell lung cancer were treated with mRNA-4157 as a standalone monotherapy, while those with melanoma were treated with the vaccine and Keytruda. All patients experienced at least one treatment-emergent side effect, with no grade 4 (life-threatening) or 5 (deadly) or dose-limiting toxicities.

The most frequent treatment-emergent side effects across both patient groups included fatigue (10 patients), pyrexia (fever, nine patients) and injection site pain (six patients), with the only grade 3 (severe) treatment-related event, fatigue, experienced by one patient.

KEYNOTE-603, with an estimated total enrollment of 242 patients, is expected to be completed in June 2025, according to its listing on clinicaltrials.gov.

“This study has important implications beyond skin and lung cancer,” Gainor said. “Over the last 15 years, melanoma and skin cancers have served as prototypical disease states for which immunotherapies play important roles.”

Vaccines such as mRNA-4157 instruct the body to produce a specific protein that triggers an immune response in a patient’s body, according to the Centers for Disease Control and Prevention. Once a mutation is identified, a personalized vaccine has to be made for each patient, experts have previously explained to CURE®.

“It basically generates an immune cell response specifically against things that are only in the tumor and not in the normal tissue,” Dr. Jeffrey S. Weber, the deputy director of Perlmutter Cancer Center and co-author of the Cancer Discovery study, told CURE® earlier this year. “… It gives the body a chance to mount a specific immune response against those very specific neoantigens. And the [Keytruda] amplifies the response.”

Previous clinical trial findings have shown mRNA-4157, also known as V940, combined with Keytruda to reduce the risk of melanoma recurrence or death by 44% compared with treatment with Keytruda alone.

According to the National Cancer Institute, mRNA-4157 is currently being evaluated in seven clinical trials, with Gainor noting that the vaccine is now being explored in renal cell carcinoma, urothelial carcinoma and cutaneous squamous cell carcinoma as well.

“The next step will be to validate these studies in randomized, phase 3 trials. Indeed, phase 3 trials evaluating mRNA-4157 as adjuvant therapy are now ongoing in lung and melanoma,” he said.

The Food and Drug Administration granted the mRNA-4157 and Keytruda combination a Breakthrough Therapy designation for the postsurgical treatment of patients with high-risk melanoma following complete resection in 2023. Breakthrough Therapy designation “is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s),” according to the FDA’s website.

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