Tedopi Vaccine Shows Positive Survival in HLA-A2-Positive Advanced NSCLC

The immunotherapeutic vaccine OSE-2101 (Tedopi) demonstrated a favorable 12-month survival rate as second- or third-line treatment of patients with HLA-A2-positive advanced non—small cell lung cancer (NSCLC), meeting the primary end point of overall survival (OS) in the phase III Atalante 1 study, according to a press release from the drug developer, OSE Immunotherapeutics, Inc.¹

“We are very pleased with these positive results for Tedopi in Step-1 and with a 10% absolute difference in 12-month survival rate versus chemotherapy in NSCLC patients after failure of checkpoint inhibitor treated in Atalante 1 Step-1 trial. This outcome confirms the therapeutic value of our neoepitope product in a patient population for whom there are no registered product today and who needs new therapeutic options,” said Alexis Peyroles, chief executive officer, OSE Therapeutics, Inc, in a statement.

In 29 of 63 patients, the 12-months survival rate was 46% with a lower limit of 33% (95% CI, 33% -59%). The results were higher than the pre-specified futility boundary of 25%. This achievement marks the completion of step 1 of the 2-step study.

The purpose of the Atlante-1 study was to present a new treatment strategy for patients who progress on an immune checkpoint inhibitor.²To determine whether OSE-2101 is an effective strategy, progression-free survival, objective response rate, disease control rate, duration of response, quality of life and safety were assessed as secondary end points.

Early findings from Atlante-1 were presented at the 2019 American Association for Cancer Research (ACCR) Annual Meeting. At the time, 18 patient were enrolled and treated with OSE-2101 lasted between 4.9 months to over 12 months. It was reported that 1 patient had a partial response to treatment, and 2 patients had stable disease. Additionally, the safety profile was considered manageable. Only 1 patient who was included in the analysis withdrew as a result of toxicity.³

Based on these early results, the investigators concluded that administering OSE-2101 in patients with HLA-A2 positive advanced NSCLC after failure to previous immune checkpoint inhibitor therapy as third-line treatment can have long-term clinical benefit.

In the ongoing Atlante-1 trial, eligible patients are randomized 2:1 to receive OSE-2101 or standard of care (SoC), which is docetaxel or pemetrexed. OSE-2101 is administered as a subcutaneous 1 ml dose every 3 weeks for 6 cycles followed by every 8 weeks, then every 12 weeks. For patients receiving SoC, docetaxel was given 75 mg/m²or pemetrexed 500 mg/m²was administered every 3 weeks. All treatments in the study are continued until progression, intolerable toxicity, or consent withdrawal.

Due to the spread of the coronavirus disease 2019, patient screening and accrual has been suspended, and Step-2 of Atlante-1 has been cancelled. The decision was a response to recommendations from an Independent Data Monitoring Committee and the study’s Steering Committee. OSE Therapeutics plans to further analyze the efficacy and safety observed with Step-1 of the study.¹

“Based on these positive results, we are now eager to engage in discussions with regulatory authorities to evaluate Tedopi’s current clinical results and agree upon the best options for further development to maximize on the product’s positive data in terms of benefit/risk ratio. In parallel, given the significant value added by positive Step-1 results, we continue exploring potential partnership opportunities for Tedopi,” said Peyroles.

References

1. Phase 3 clinical trial of Tedopi®: OSE Immunotherapeutic announces positive top-line results for step-1 of its trial ‘Atalante 1’ in non-small cell lung cancer [news release]. Nantes, France: OSE Therapeutics, Inc; April 2, 2020.https://bit.ly/2JxFN1V. Accessed April 2, 2020.
2. Felipe E, Besse B, Dziadzioszko R, et al. 1592TiP - ATALANTE-1 randomized phase III trial, OSE-2101 versus standard treatment as second or third-line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients.Ann Oncol.2019 (30); 658. Doi: 10.1093/annonc/mdz260.114.
3. Viteri S, Vanel FR, Higers W, et al. Early signs of activity of Tedopi OSE2101, a multiple neoepitope vaccine, in a phase 3 trial in advanced lung cancer patients after failure to previous immune checkpoint inhibitors ATALANTE-1. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 946.