A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell...

Area of Science:

• Oncology
• Immunology
• Vaccinology

Background:

• Neoantigens, derived from cancer cell mutations, are crucial for T cell-mediated anti-tumor immunity.
• Targeting neoantigens presents a promising strategy for cancer immunotherapy.

Purpose of the Study:

• To evaluate the safety and immunogenicity of a personalized neoantigen vaccine (NEO-PV-01) in combination with PD-1 blockade.
• To assess treatment efficacy in patients with advanced melanoma, non-small cell lung cancer, and bladder cancer.

Main Methods:

• An open-label, phase Ib clinical trial involving 82 patients with advanced solid tumors.
• Administration of NEO-PV-01 vaccine concurrently with PD-1 blockade therapy.
• Monitoring for safety, neoantigen-specific T cell responses (CD4+ and CD8+), T cell phenotype, tumor trafficking, and epitope spread.

Main Results:

• The combination regimen was safe, with no observed treatment-related serious adverse events.
• All patients exhibited de novo neoantigen-specific CD4+ and CD8+ T cell responses post-vaccination.
• Vaccine-induced T cells demonstrated a cytotoxic phenotype, tumor trafficking, and tumor cell killing capabilities.
• Epitope spread to non-vaccine neoantigens was detected, indicating a broader immune response.

Conclusions:

• The combination of NEO-PV-01 and PD-1 blockade is safe and immunogenic in patients with advanced solid tumors.
• This therapeutic approach effectively stimulates anti-tumor T cell immunity.
• The findings support further clinical investigation of this personalized cancer vaccine strategy.