Novel Cancer Vaccine Meets Primary, Secondary End Points in Resected Melanoma

The primary end point of recurrence-free survival (RFS) and secondary end point of distant metastasis-free survival (DMFS) was met in the phase 3 INTerpath-001 trial (NCT05933577) assessing intismeran autogene (V940) plus pembrolizumab (Keytruda) for patients with completely resected stage IIB to IV melanoma, according to a press release from Merck.¹

During the prespecified interim analysis, the combination showed a statistically significant and clinically meaningful improvement in RFS and DMFS vs pembrolizumab alone. Patients assessed in the trial included those with resected stage IIB, IIC, or IV cutaneous melanoma who had not received prior treatment with systemic therapy. Overall survival will be evaluated for future trial readouts.

Regarding safety, results were consistent with previously reported outcomes for the combination. No new safety signals occurred. These data will be presented at an upcoming medical meeting, as well as shared with regulatory authorities.

V940 is a novel investigational mRNA-based individualized neoantigen therapy (INT). The results are among the first for a phase 3 trial assessing an INT that demonstrated a clinically meaningful improvement compared with pembrolizumab alone. Currently, pembrolizumab is the current standard of care immunotherapy in the adjuvant setting for patients with resected melanoma.

“Today’s results represent a landmark moment for adjuvant melanoma treatment. This is the first phase 3 study to show that [V940], a treatment designed based on the unique mutational ‘fingerprint' of a patient's own tumor, given in combination with pembrolizumab can reduce the risk of recurrence or death in patients with completely resected stage IIB to IV melanoma compared with [pembrolizumab] alone,” Georgina Long, BSc, PhD, MBBS, FRACP, FAHMS, AAHMS, FAA, FASCO, the study’s principal investigator and medical director of Melanoma Institute Australia, chair of Melanoma Medical Oncology and Translational Research at the University of Sydney, said in the press release.¹ “[V940] in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”

In 2024, the INTERpath-001 trial was presented during the American Society of Clinical Oncology (ASCO) Annual Meeting as a trial in progress.² At the time, 1089 patients were expected to enroll and be randomly assigned 2:1 to either receive pembrolizumab at 400 mg plus V940 at 1 mg or pembrolizumab plus placebo. Pembrolizumab would be given intravenously every 6 weeks and V940 would be given intramuscularly every 3 weeks. Treatment was expected to continue for up to 9 doses or until unacceptable toxicity or patient withdrawal.

Additionally, data presented at the 2026 ASCO Annual Meeting of the phase 2b KEYNOTE-942 study (NCT03897881) trial assessing V940 plus pembrolizumab showed a 49% reduction in the risk of recurrence or death (HR, 0.51; 95% CI, 0.294-0.887).³ Additionally, there was a 59% reduction in the risk of distant metastasis or death (HR, 0.411; 95% CI, 0.200-0.843) vs pembrolizumab alone.

Patients were included in the trial if they had surgically resected and histologically/pathologically confirmed diagnosis of stage IIB or IIC, III, or IV cutaneous melanoma; had not received any prior systemic therapy for their melanoma beyond surgical resection; no more than 13 weeks have passed between final surgical resection that rendered the patient disease-free and the first dose of pembrolizumab; were disease free when providing documented consent for the study; and those with HIV must have well controlled HIV and be on anti-retroviral therapy.⁴

Patients were excluded from treatment if they had ocular or mucosal melanoma; had cancer that had spread to other parts of their body and could not be removed with surgery; have heart failure within the past 6 months; have received prior cancer therapy for another vaccine; have another known cancer that had spread to other parts of the body or had needed treatment within the past 3 years; or has severe reaction to study medication or any of their substance that is used in treatment preparation.

“These first phase 3 findings for [V940] in combination with [pembrolizumab] as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment. We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated,” Dean Y. Li, MD, PhD, president of Merck Research Laboratories, concluded.¹

References

1. Merck and Moderna announce phase 3 INTerpath-001 trial of intismeran autogene plus KEYTRUDA® met endpoints of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma. News release. August 19, 2026. Accessed August 19, 2026. https://tinyurl.com/yxe3d24n
2. Weber JS, Luke JJ, Carlino MS, et al. INTerpath-001: pembrolizumab with V940 (mRNA-4157) versus pembrolizumab with placebo for adjuvant treatment of high-risk stage II-IV melanoma. J Clin Oncol. 2024;42(suppl 16):TPS9616. doi: 10.1200/JCO.2024.42.16_suppl.TPS9616
3. Carlino MS, Khattak A, Meniawy T, et al. Individualized neoantigen therapy intismeran autogene (intismeran) plus pembrolizumab (pembro) in resected melanoma: 5-year update of the KEYNOTE-942 study. J Clin Oncol. 2026;44(suppl 16):9500. doi:10.1200/JCO.2026.44.16_suppl.9500
4. A clinical study of intismeran autogene (V940) plus pembrolizumab in people with high-risk melanoma (V940-001). ClinicalTrials.gov. Updated September 24, 2025. Accessed August 19, 2026. https://tinyurl.com/3wjyjhw9