Personalized cancer vaccines show promising clinical results

Moderna and MSD present long-term ASCO data showing reduced melanoma recurrence

Development Expands into NSCLC, renal cell carcinoma, and other solid tumors…follow up clinical trials gain momentum

Personalized messenger RNA (mRNA)-based cancer vaccines are drawing increasing attention as a potential new treatment strategy for melanoma after long-term follow-up data confirmed their ability to reduce disease recurrence.

Particularly noteworthy is the combination of personalized cancer vaccines with the immuno-oncology drug Keytruda (pembrolizumab). Clinical data demonstrated a long-term reduction in recurrence risk among high-risk melanoma patients following surgery, highlighting the growing clinical feasibility of personalized cancer vaccine approaches.

According to industry sources, Moderna and MSD presented five-year follow-up results from the Phase IIb KEYNOTE-942/mRNA-4157-P201 study, which evaluated patients with high-risk stage III and IV melanoma, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

The trial compared adjuvant therapy consisting of intismeran autogene (mRNA-4157/V940), an investigational personalized mRNA neoantigen therapy, plus Keytruda versus Keytruda alone in patients who had undergone complete surgical resection.

At a median follow-up of 60.3 months, the combination therapy continued to improve the primary endpoint of recurrence-free survival (RFS) and reduced the risk of recurrence or death by 49% compared with Keytruda monotherapy.

The regimen also demonstrated significant benefit in the key secondary endpoint of distant metastasis-free survival (DMFS), reducing the risk of distant metastasis or death by 59%.

An exploratory analysis of overall survival (OS) suggested a trend toward improved survival with the combination therapy. However, as there are not yet sufficient cases within the follow-up period, an evaluation of long-term survival benefits is expected to require further observation.

MSD’s immuno-oncology drug, ‘Keytruda’

In fact, additional analysis showed that the combination therapy promoted the generation and expansion of new T-cell clonotypes compared with Keytruda alone.

Long-term follow-up revealed that the combination group had a ratio of newly expanded T-cell clones that was approximately twice as high. This increase in immune response was particularly pronounced among patients who remained recurrence-free. These findings support the hypothesis that personalized neoantigen-based therapies can activate meaningful anti-tumor immune responses.

The safety profile remained consistent with previous analyses. The most commonly reported adverse events included fatigue, injection site pain, and chills, and most were Grade 1 or 2 in severity. The incidence of immune-related adverse events was comparable to that observed with Keytruda alone, suggesting that the addition of the vaccine did not substantially increase toxicity.

Unlike infectious disease prevention vaccines, cancer vaccines are not intended to prevent cancer development. Instead, they are individualized therapeutic approaches tailored to each patient's tumor characteristics. The process involves analyzing tumor-specific genetic mutations and neoantigens and then designing a treatment that stimulates an immune response against those unique targets.

Intismeran autogene is specifically designed using mutation data obtained from a patient's tumor DNA and can incorporate up to 34 personalized neoantigens. The therapy is intended to activate T-cell-mediated immune responses, enabling the immune system to recognize and eliminate cancer cells more effectively.

Major pharmaceutical and biotechnology companies are increasingly focusing on personalized cancer vaccines as a means of enhancing treatment outcomes rather than preventing disease. The strategy centers on combining cancer vaccines with immuno-oncology drugs and potentially with other therapeutic platforms such as antibody-drug conjugates (ADCs) to maximize anti-tumor efficacy.

Moderna and MSD are currently evaluating the combination of intismeran autogene and Keytruda not only in melanoma but also in a variety of solid tumors, including non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma. A total of nine Phase II and Phase III clinical programs are currently underway. Patient enrollment has already been completed for certain melanoma and renal cell carcinoma studies, and follow-up clinical trials are also continuing for non-small cell lung cancer as adjuvant therapy and perioperative strategies.