EVX-01 plus pembrolizumab generated an overall response rate of 75% and durable T-cell responses in advanced melanoma.
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
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.
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
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.
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.
