An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma

Area of Science:

• Oncology
• Immunology
• Vaccine Development

Background:

• Cancer vaccines aim to stimulate targeted immune responses but have shown limited success in late-stage, treatment-refractory tumors.
• Advanced melanoma patients, particularly those who have progressed on checkpoint inhibitors, represent a significant unmet medical need.

Purpose of the Study:

• To evaluate the safety and efficacy of melanoma FixVac (BNT111), an RNA-liposomal nanoparticle (RNA-LPX) vaccine, in patients with advanced melanoma.
• To assess the immune response induced by melanoma FixVac, alone or in combination with PD1 blockade, in checkpoint-inhibitor (CPI)-experienced patients.

Main Methods:

• An ongoing, first-in-human, dose-escalation Phase I trial (Lipo-MERIT) is evaluating melanoma FixVac in advanced melanoma patients.
• The study involves intravenous administration of the RNA-LPX vaccine targeting four prevalent, non-mutated, tumor-associated antigens.
• An exploratory interim analysis included patients who had previously received checkpoint inhibitor therapy.

Main Results:

• Melanoma FixVac, alone or combined with PD1 blockade, demonstrated durable objective responses in CPI-experienced patients with unresectable melanoma.
• Clinical responses were associated with the induction of robust CD4+ and CD8+ T cell immunity against vaccine antigens.
• Antigen-specific cytotoxic T-cell responses in responders reached magnitudes comparable to adoptive T-cell therapy and were durable.

Conclusions:

• RNA-liposomal nanoparticle (RNA-LPX) vaccination represents a potent immunotherapy for patients with CPI-experienced melanoma.
• The findings suggest that non-mutant shared tumor antigens are viable targets for developing effective cancer vaccines.
• Melanoma FixVac shows promise for improving outcomes in advanced melanoma, particularly in patients resistant to current therapies.