Long-term clinical outcomes of AST-021p, an HSP90 peptide vaccine, in advanced solid tumors: Follow-up results of the phase I CornerStone-002 trial

초록

Background: AST-021p is a novel peptide-based therapeutic cancer vaccine targeting MHC class II epitopes from heat shock protein 90 (HSP90), a tumor-associated antigen overexpressed in solid tumors. It is designed to induce antigen-specific CD4+ Th1 responses and facilitate downstream CD8+ Tc activation via cross-priming. This open-label, dose-escalation phase 1 trial (NCT04864418) evaluated safety, tolerability, and immunogenicity, with exploratory assessment of long-term clinical outcomes in patients with advanced solid tumors lacking standard options. Methods: Patients received AST-021p intradermally in four sequential dose cohorts (1.2, 2.4, 3.6, 4.8 mg) using a 3+3 design. Each cycle comprised three biweekly priming vaccinations, followed by optional monthly boosters until progression or withdrawal. Peripheral blood mononuclear cells were collected at baseline, week 4, and week 8 for IFN-γ ELISpot assays targeting two peptides (p4, p5). Immune responders were predefined as those with increased antigen-specific IFN-γ secretion from baseline. Safety was assessed per CTCAE v5.0. Long-term follow-up evaluated progression-free and overall survival. Results: Twenty-two patients treated. AST-021p was well tolerated across all dose levels, with no grade ≥3 treatment-related adverse events. The most frequent related event was grade 1–2 injection site reaction (68.2%). Immunogenicity showed a dose-dependent trend, with the 3.6 mg cohort achieving the highest responder rate (88%), followed by 4.8 mg (83%) and 2.4 mg (50%). Responders showed marked expansion of CD4+ memory T cells (Tem, Tcm). Median follow-up: 8.5 (1.6–17.5), 7.1 (1.4–23.5), and 17.7 (4.5–29.8) months for cohorts 1–3, respectively. Several responders maintained stable disease beyond 12 months. Conclusions: AST-021p demonstrated favorable safety, tolerability, and immunogenicity in advanced solid tumors. The 3.6 mg dose was selected as the recommended phase 2 dose based on safety and immune durability. These results support further phase 2 evaluation of biomarker-enriched populations to confirm efficacy. Data highlight AST-021p’s potential as a safe, durable immunotherapy for patients with limited treatment options.