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Treatment with the combination of the personalized peptide-based neoantigen vaccine EVX-01 and pembrolizumab (Keytruda) led to T-cell responses and generated durable disease control in patients with previously untreated, stage III or IV unresectable melanoma, according to 2-year follow-up data from a phase 2 trial (NCT05309421).¹

Data presented at the 2025 ESMO Congress demonstrated that evaluable patients (n = 16) achieved an overall response rate (ORR) of 75%. At 24 months of follow-up, responses persisted in 11 of the 12 responders. Four patients had discontinued the study, including 3 patients with progressive disease and 1 partial responder who experienced intracranial hemorrhage. Notably, deepened responses were reported in 7 of 13 evaluable patients, translating to a conversion rate of 54%.

Potent, specific T-cell responses were reported in all patients. The AI Immunology platform successfully predicted T-cell responses at a rate of 81%, based on immunogenic vaccine neoantigens (n = 85) and non-immunogenic vaccine neoantigens (n = 20) detected. T-cell responses were induced during the priming of EVX-01 and were sustained over the first 2 years of the study, according to lead study author Adnan Khattak, MBBS, FRACP, PhD.

“These findings support the ongoing development of [EVX-01 plus pembrolizumab], and further discussions are ongoing with sponsors and regulatory authorities,” Khattak said during the presentation. Khattak is a professor, a specialist physician in medical oncology, and director at the Fiona Stanley Hospital Cancer Clinical Trials Unit at Hollywood Private Hospital of Ramay Health Care in Nedlands, Western Australia.

Why Is EVX-01 Being Investigated in Advanced Melanoma?

Although the incorporation of immunotherapy-based regimens has led to improved outcomes for patients with advanced melanoma, Khattak explained that an unmet need remains in this setting.

To create the personalized neoantigen vaccine EVX-01, DNA and RNA sequencing is conducted on patient blood and tumor samples. After the AI Immunology platform identifies 7 to 10 patient-specific antigens that are optimal for each individual, peptide formulation and EVX-01 formulation is completed.

In January 2023, the FDA granted fast track designation to EVX-01 plus pembrolizumab for the treatment of patients with metastatic melanoma.²

How Was the Phase 2 Trial of EVX-01 Plus Pembrolizumab Designed?

The phase 2 study enrolled patients at least 18 years of age with histologically confirmed metastatic or unresectable stage III/IV melanoma who were not amenable to local therapy.³ Those with uveal or ocular melanoma were excluded, and prior treatment with an immune checkpoint inhibitor was not allowed. BRAF mutation testing was required prior to enrollment and prior BRAF-targeted therapy was permitted as first-line therapy. Those harboring BRAF V600E mutations were allowed to enroll without prior treatment with a BRAF inhibitor if they had a lactate dehydrogenase (LDH) level below the local upper level of normal, had no clinically significant tumor-related symptoms per investigator discretion, and did not have rapidly progressing metastatic melanoma.

Other key inclusion criteria for all patients comprised measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

All enrolled patients received pembrolizumab at 400 mg once every 6 weeks from week 0 through week 102.¹ After EVX-01 manufacturing in week 0, priming doses of the neoantigen vaccine were administered at weeks 12, 14, 16, 18, 20, and 22, followed by boosting doses at weeks 30, 42, 54, and 78. Notably, the manufacturing success rate for EVX-01 was 100%.

The study’s primary end points were ORR, duration of response, and conversion rate, defined as patients who converted from stable disease to a response, or a partial response to a complete response per RECIST 1.1 criteria.

All enrolled patients were White, and the majority were male (69%), at least 65 years of age (56%), had an ECOG performance status of 0 (94%), had stage IV disease (87.5%), and had normal LDH levels (63%). Patients had a mean of 2.1 target lesions (range, 1-5) and 1.1 non-target lesions (range, 0-4). Half of patients had a PD-L1 expression of more than 5%, 25% had a PD-L1 expression of less than 5%, and 25% had unknown PD-L1 status. Half of patients also harbored BRAF mutations; 38% and 13% had negative and unknown BRAF statuses, respectively.

What Safety Data Were Reported for EVX-01 Plus Pembrolizumab at 2 Years of Follow-Up?

Regarding toxicities specific to EVX-01, no grade 3 or higher adverse effects (AEs) were reported. Two grade 2 AEs related to the vaccine occurred, along with 18 grade 1 AEs. The combination therapy was linked to grade 3 pancreatitis and grade 4 diabetic ketoacidosis in 1 patient.

Disclosures: Khattak reported receiving research grants from the Raine Foundation Translational Research Fellowship, NHMRC, Spinnaker Health Research Foundation, MSD, and Cancer Council WA; receiving travel sponsorship from BMS, MSD, Roche, Merck, Amgen, Evaxion, and Moderna; receiving speaker honoraria from Merck Serono, BMS, and MSD; and serving on an advisory board for BMS, MSD, and OCR.

References

1. Khattak A, Ascierto P, Cimminiello C, et al. EVX-01, a personalized cancer vaccine, induces potent T-cell responses and durable disease control in advanced melanoma: 2-year follow-up. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 1516MO.
2. Evaxion receives FDA fast-track designation for personalized cancer immunotherapy. News release. Evaxion Biotech. January 19, 2023. Accessed October 27, 2025. https://evaxion.ai/investors/press-releases/?press_release_id=7481
3. A single arm trial evaluating the efficacy and safety of EVX-01 in combination with pembrolizumab in adults with unresectable or metastatic melanoma. ClinicalTrials.gov. Updated September 22, 2025. https://clinicaltrials.gov/study/NCT05309421