Results from the randomised Phase 3 clinical trial (Atalante-1) on T-cell epitope cancer vaccine in HLA-A2 positive patients with advanced or metastatic NSCLC in monotherapy in third-line NSCLC with secondary resistance to immune checkpoint inhibitors (ICI) were published in Annals of Oncology.

T-cell epitope cancer vaccine is a novel T-cell epitope-based cancer vaccine targeting five tumour-associated antigens, an activating and differentiated off-the-shelf immunotherapy expanding tumour-specific T-lymphocytes in HLA-A2 cancer patients. The article features positive data from the randomised international Phase 3 study showing that novel T-cell epitope cancer vaccine improves overall survival with a better safety and quality of life profile in monotherapy compared to chemotherapy in HLA-A2 positive patients with advanced or metastatic NSCLC who have progressed at least 12 weeks after sequential treatment with chemotherapy and immune checkpoint inhibitors (ICI).

Prof. Benjamin Besse, Director of Clinical Research at Gustave Roussy Institute (IGR, Villejuif, France), and Principal Investigator of the Atalante-1 clinical trial, commented: “T-cell epitope cancer vaccine is the first cancer vaccine to demonstrate positive results on survival in a randomised Phase 3 trial in advanced and metastatic NSCLC cancer patients in 3rd line. A significant reduction of the risk of death by 41% was achieved with a better safety profile and a maintained quality of life. This study, conducted in patients with secondary resistance to immunotherapy, compared T-cell epitope cancer vaccine monotherapy with standard-of-care docetaxel or pemetrexed chemotherapies. Further evaluation is clearly warranted in a second line of treatment of advanced and metastatic NSCLC, to potentially make this cancer vaccine available to hard-to-treat patients in failure and with high medical needs.”

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: “T-cell epitope cancer vaccine is the most advanced therapeutic cancer vaccine in clinical development. These Phase 3 data, demonstrating the promising effects, have now been validated in the internationally recognised journal ‘Annals of Oncology', a major achievement for all involved so, in particular, we’d like to thank warmly the investigators, the patients and their families for their commitment. This Phase 3 positive monotherapy data and moreover the recently announced positive Phase 1 and 2 results using other personalised cancer vaccines in combination to treat resected melanoma or pancreatic cancer patients, highlight the promise of this new therapeutic class of vaccines. The clinical value of our results, re-activating specifically the anti-tumour immune responses, is particularly interesting in patients showing immune escape from checkpoint inhibitors. The confirmatory pivotal Phase 3 trial in preparation is planned to support the regulatory registration of T-cell epitope cancer vaccine in secondary resistance to immune checkpoint inhibitors, this time in second-line NSCLC treatment.”

Main results of the first Phase 3 clinical trial of T-cell epitope cancer vaccine in HLA-A2+ patients with NSCLC

This Phase 3 clinical trial has demonstrated a significant therapeutic benefit in patients with secondary resistance(1) to immune checkpoint inhibitors (ICI) defined as patients with failure to platinum-based chemotherapy followed by a minimum of 12 weeks ICI treatment (main analysis of the trial). T-cell epitope cancer vaccine demonstrated a favourable benefit/risk ratio versus standard of care (SoC) docetaxel or pemetrexed in advanced HLA-A2+ NSCLC patients with secondary resistance to ICI.

The main results were:

Improved efficacy

1. Overall survival (primary endpoint) was statistically significantly improved for T-cell epitope cancer vaccine:HR=0.59 (95% CI: 0.38, 0.91) in favour of the T-cell epitope cancer vaccine arm, reduced risk of death by 41%; 44.4% overall survival rate at 1 year with T-cell epitope cancer vaccine versus 27.5% with chemotherapy. A clinically meaningful gain in median overall survival of 3.6 months in favour of the T-cell epitope cancer vaccine arm with T-cell epitope cancer vaccine OS at 11.1 months versus 7.5 months for SoC (p=0.017).
2. Post-progression survival was also significantly longer in the T-cell epitope cancer vaccine arm (7.7 months versus 4.6 months; p=0.004, HR=0.46).

Improved safety profile and Quality of Life

1. The ECOG performance status(2), of maintained general health condition with time to ECOG deterioration was significantly longer in the T-cell epitope cancer vaccine arm (9.0 months versus 3.3 months; p=0.006; HR=0.43).
2. A better quality of life was observed with T-cell epitope cancer vaccine (p= 0.04). (Global health status: p=0.045; Role Functioning: p=0.025).
3. A good tolerance profile of T-cell epitope cancer vaccine with fewer Severe Adverse Events grade 3-5 (T-cell epitope cancer vaccine 38% vs SoC 68%, p<0.001). No Treatment-Emergent Adverse Effects of concern in the T-cell epitope cancer vaccine arm.

Source: Halsin Partners