DUBLIN – Ose Immunotherapeutics SA finds itself in the difficult place of hitting the primary endpoint of the first part of a phase III trial of Tedopi, a therapeutic vaccine, in non-small-cell lung cancer (NSCLC) while having to terminate the study without completing the crucial second part. Instead, the Nantes, France-based firm plans to finish the analysis of Step-1 of the Atalante 1 trial and then to engage with regulatory authorities to determine the next step in the program. “We expect the agencies will ask for a confirmatory trial,” CEO Alexis Peyroles told BioWorld.

The Step-1 portion of the trial was designed to demonstrate that Tedopi could hit a certain efficacy threshold, before progressing to the pivotal part of the study, which was designed to demonstrate an overall survival benefit. All of the patients had metastatic disease and had progressed after checkpoint (PD-1/PD-L1) inhibitor failure. Of 63 patients who received Tedopi as a monotherapy during Step-1, 29 remained alive after one year of follow-up, implying a 12-month survival rate of 46%. The lower limit of the 95% confidence interval [33% – 59%] was above the prespecified 25% futility threshold. In the control arm, the 12-month survival rate was 36% (13/36).

The first part of the study was not powered to demonstrate a statistically significant difference between the two arms, however. A statistically insignificant 10% improvement over chemotherapy is not, in itself, evidence of a major breakthrough. However, there is little clinical data in this patient population, Peyroles said. But the crucial overall survival data that would ultimately establish whether Tedopi has clinical utility in this population will not be forthcoming.

Alexis Peyroles, CEO, Ose

Ose has shut down the second part of the study, on the recommendation of the independent data monitoring committee and the trial’s steering committee. Given the particular vulnerability of patients with metastatic NSCLC, any data from that portion of the trial would inevitably be compromised. “The situation is very specific, and it was not anticipated,” Peyroles said. Although Ose has already recruited and treated about 100 of a planned 225 patients, it is unlikely that they will be able to attain sufficient follow-up to generate an unbiased dataset. “You will be unable to evaluate it correctly,” Peyroles said. The company will, however, continue to collect the data on an exploratory basis.

It aims to complete the Step-1 analysis over the coming months and to engage with the drug regulators once the COVID-19 pandemic is brought under control, in order to establish its next steps. “When exactly, I really don’t know. It depends on COVID-19,” he said. The company anticipates another phase III study. “With that, we could find a partner to help finance the trial and get it to registration,” he said.

Tedopi is a product with a long clinical history behind it. The peptide vaccine, which consists of nine HLA-A2-binding epitopes derived from five common tumor-associated antigens and the universal pan-DR T-helper cell epitope, was originally in development at Epimmune over a decade ago. The advent of checkpoint inhibitor therapies has given those early immunotherapies a new lease on life, Peyroles said. Tedopi is also undergoing a phase II combination trial with the PD-1 inhibitor Opdivo (nivolumab, Bristol Myers Squibb Co.) in pancreatic cancer.

The three-arm study is comparing Tedopi alone with Tedopi plus Opdivo and the Folfiri chemotherapy regimen. The plan is to recruit 50 patients for each arm, but to conduct an interim analysis based on the first 20 in each arm. The COVID-19 pandemic may disrupt plans for an interim readout, however. “It’s too soon to say if we’ll have it or not,” Peyroles said.

The company released the Tedopi news April 1 after the close of trading on Euronext Paris. Its stock (Paris:OSE) had ended the day at €2.99 (US$3.27), a drop of 10% on the previous close. The company, which has partnerships with Ingelheim, Germany-based Boehringer Ingelheim GmbH and Suresnes, France-based Les Laboratoires Servier SAS, exited 2019 with €25.8 million in cash and is funded into the first quarter of 2021.