Patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of the ATALANTE-1 study was to evaluate its efficacy and safety in these patients.
OSE2101 is a T-specific immunotherapy designed to induce cytotoxic T lymphocytes (CTLs) against five tumour-associated antigens (TAAs) frequently overexpressed in non-small cell lung cancer (NSCLC) (HER-2/neu, CEA, MAGE 2, MAGE 3, and p53). This therapeutic vaccine is composed of nine synthetic peptides from these TAAs that are present in lung cancer cells in the human leukocyte antigen (HLA)-A2 phenotype, found in up to 45% of the population. A 10th pan-DR peptide has been added to elicit the T helper lymphocyte immune response. These multi-chemically modified epitopes from the five TAAs in the OSE2101 cancer vaccine represent an ideal target to break immune tolerance in resistant tumours. They generate a novel and specific activation of CTLs that attack recognised tumour cells, as measured by increased IFN-γ production. The vaccine promotes an increase in TAA presentation, the priming and activation of T cells and the recognition of cancer cells expressing the TAA, thereby invigorating antitumor-specific immune responses (specific CD8+ T cells) and possibly the overall T response through CD4+ activation.
METHODS
ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of cancer vaccine OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomised (2:1) to OSE2101 or SoC (docetaxel or pemetrexed). The primary endpoint was overall survival (OS). In April 2020, at the time of interim analysis, a decision was taken to prematurely stop the accrual due to COVID-19. The final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks.
FINDINGS
In total, 219 patients were randomly assigned to receive OSE2101 (n=139) or SoC (n=80). Of those, 118 had secondary resistance to sequential ICB. The results revealed a non-significant OS benefit with OSE2101 over SoC (HR[95%CI]: 0.86 [0.62-1.19], p=0.36). In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC (11.1 versus 7.5 months; HR[95% CI]: 0.59 (0.38-0.91), P=0.017), and significantly improved post-progression survival (HR: 0.46, P=0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR: 0.43, P=0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P=0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P=0.002).
CONCLUSION
In summary, the ATALANTE-1 study suggests that T-cell vaccination with OSE2101 monotherapy may improve survival in patients with HLA-A2-positive advanced NSCLC who have progressed at least twelve weeks after sequential treatment with CT and ICB. This evidence is a benchmark to explore this strategy in other clinical settings with secondary resistance to immunotherapy. Further evaluation of this population is warranted.1
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