Clinical Trials

Date: 2017-12-07

Type of information: update on patient enrollment

phase: 3

Announcement: update on patient enrollment

Company: OSE Pharma (France) now OSE Immunotherapeutics

Product: Tedopi® (OSE2101)

Action mechanism:

• immunotherapy product. Tedopi® (OSE2101) targets five tumour associated antigens (TAA), selected because their presence is linked to a poor prognosis and the severity of various cancers. Tedopi® contains ten optimized epitopes, or “neoepitopes”, designed on the binding of HLA-A2 and TCR. These neo-epitopes generate strong specific T cytotoxic responses that fight cancer and prevent tumour escape. These five tumor antigens (HER-­2/neu, p53, CEA, MAGE-2 and MAGE-­3) are expressed in various tumors related to poor prognosis and even poorer when associated. Since February 2013, OSE2101 has been granted orphan drug status by the FDA for the treatment of NSCLC in patients expressing HLA-­A2.

Disease: non-­small cell lung cancer

Therapeutic area: Cancer - Oncology

Country: Czech Republic, France, Hungary, Italy, UK, USA

Trial details:

• This international Atalante 1 Phase 3 registration study is aimed at evaluating the benefits of Tedopi® as compared to current standard chemotherapies (docetaxel or pemetrexed, both approved second line therapies). Tedopi® is administered as second-line (after failure of platinium based therapy) or third-line (after failure of immune checkpoint inhibitors) of treatment in HLA-A2 positive patients; HLA-A2 is a key receptor for the cytotoxic T-immune response in those patients diagnosed with stage IIIB (locally advanced) or IV (metastatic) NSCLC. The primary endpoint of Atalante1 is overall survival. The study will include 500 patients enrolled at 70 European and U.S. investigational clinical sites. The trial is expected to be completed in 2018, provided that the recruitment of patients, their observed survival and the safety of the product meet the strict criteria set for this study. The clinical trial Atalante 1 is being conducted internationally by a steering committee co-chaired by Doctor Benjamin Besse, Head of the Thoracic Pathology Committee at the Institut Gustave Roussy (Villejuif), and Giuseppe Giaconne, Professor of Oncology, Medicine and Pharmacology at the Georgetown Lombardi Comprehensive Cancer Center in Washington. Of the 500 patients to be included in the clinical trial, around 80% will be recruited by European clinical centers, and the remaining 20% by US American centers. (NCT02654587)

Latest news:

• • On December 7, 2017, OSE Immunotherapeutics  announced that the Independent Data Monitoring Committee (IDMC) has recommended to the trial’ssteering committee that accrual of the Tedopi® Phase 3 trial for the treatment of advanced non-small cell lung cancer (NSCLC) could resume with a specified new recruitment strategy focused on a subgroup of patients who have failed a previous treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICI). The PD-1/PD-L1 ICI class is becoming a new standard of care for patients with advanced NSCLC, demonstrating efficacy versus chemotherapy in first- and second-line treatment. There continue to be no safety concerns, as safety data remain similar to what was expected for Tedopi® based on the results of previous clinical trials.
• The IDMC’s most recent recommendation also includes maintaining the hold on accrual of patients who have not received prior treatment with immune checkpoint inhibitors. Following formal approval from the Competent Authorities, patient accrual will resume exclusively in the group previously defined in the protocol: patients who have previously failed an ICI treatment. This patient group represents a specific population for which there are currently no approved treatment options, and for which a significant clinical need exists.
• • On June 23, 2017,  OSE Immunotherapeutics announced that following the recommendation by IDMC (independent experts) on the phase 3 clinical study, Atalante 1, the company is temporarily pausing patient accrual while continuing treatment for patients already enrolled in order to further assess the study’s current patient profile in relation to the potential benefit of Tedopi® with more mature data. “The Company has decided to halt temporarily patient enrolment, but to continue treatment of patients already enrolled in this clinical trial, due to an emerging benefit/risk balance of the experimental treatment” said Dominique Costantini, Chief Executive Officer of OSE Immunotherapeutics. “Patients eligible for inclusion in the Atalante 1 study are cancer patients at an advanced stage who have failed a first-line treatment with chemotherapy or failed second-line therapy with checkpoint inhibitors, and enter the trial at stage of disease progression. This cancer progression may be difficult to control for some patients in the near-term due to the generally longer-term activity observed with a combination of neoepitopes, which differs from chemotherapy’s generally near-term activity.”
• Following further review of more patients’ data and additional information being available, a decision will be made for the trial continuation as such or possible amendment to include specific sub-groups of patients. The expected safety profile was observed in both treatment groups. The safety profile observed in the experimental treatment group is consistent with the one observed in the previous clinical trials of Tedopi®.
• • On January 24, 2017, OSE Immunotherapeutics announced  that the Independent Data Monitoring Committee (IDMC) for the international pivotal Phase 3 clinical study of Tedopi® for the treatment of non-small cell lung cancer (NSCLC) has unanimously recommended continuation of the trial, without asking for modifications. The  study is designed to evaluate the benefits of Tedopi® compared to current standard chemotherapies (docetaxel or premetrexed, both approved as 2nd line treatments) in HLA-A2 positive patients with stage IIIB (locally advanced) or IV (metastatic) NSCLC who have failed platinium-based therapy or 2 nd line checkpoint inhibitor therapy. As recent clinical evidence has demonstrated positive results with checkpoint inhibitors in 1st line therapy, the study population has been extended to patients who received checkpoint inhibitors either as 1st or 2nd line therapy. A second IDMC review is expected to occur in the second quarter of 2017.
• • On September 20, 2016, OSE Immunotherapeutics announced that the company will present a poster describing the updated design of the registration clinical trial Atalante 1, at the  World Conference on Lung Cancer taking place in Vienna (Austria) from December 4th to December 7th, 2016. The Atalante 1 study is now open in nine countries, in the United States and in Europe, where patient enrollment is being actively pursued.
• • On April 11, 2016, OSE Pharma announced initiation in Hungary of its Phase 3 clinical trial, Atalante 1.
• • On February 22, 2016, OSE Pharma announced enrolment and treatment of the first patients in its Atalante 1 Phase 3 trial. These first patients were enrolled at the Institut Gustave Roussy (Villejuif) and the Hospital Saint-Louis (Paris).
• • On February 4, 2016, OSE Pharma announced initiation in the United States of the Atalante 1 trial. The company’s approval of a first clinical site triggers the initiation in the United States of the global Phase 3 trial. The study was initiated in Europe in early 2016, and so the screening of eligible HLA-A2 positive patients diagnosed with NSCLC is now actively ongoing in both territories.
• • On January 6th, 2016, OSE Pharma announced  the initiation of its registration clinical trial named “Atalante 1”. This trial evaluates Tedopi®, the company’s lead product for advanced non-small cell lung cancer (NSCLC). The formal authorizations from regulatory agencies in France, Italy and Czech Republic, and the positive opinions from national ethic committees in these three countries enable the initiation of the Phase 3 trial Atalante 1. Patient enrollment is now open in these three countries and the company is expecting the same national authorizations in the remaining four European countries and in the US.
• • On November 2, 2015, Ose Pharma announced that the regulatory authorities in 7 European countries have issued a positive opinion to initiate its pivotal Phase 3 clinical trial of Tedopi® for patients diagnosed with advanced nonsmall cell lung cancer (NSCLC). These approvals will allow the pivotal Phase 3 trial of Tedopi® to start by the end of 2015. The Phase 3 clinical trial, which will include 500 patients in Europe and the United States, is expected to be completed in 2018 provided that the recruitment of patients, their observed survival and the safety of the product meet the usual criteria for this kind of trials. The trial will focus on patients diagnosed with stage IIIB (advanced) or IV (metastatic) non-small cell lung cancer (NSCLC) after at least one first line therapy failure. All patients will express HLA-A2 receptor (representing 45% of NSCLC patients). It is a key receptor for the cytotoxic T-immune response and HLA-A2 patients are the responder Tedopi® population. Tedopi® will be compared to current standard chemotherapy (docetaxel or pemetrexed, both approved in second therapy line). The primary endpoint of this trial will be overall survival (the Phase 2 study demonstrated a long survival of patients, considering how advanced their pathology was).
• • On January 29, 2015, OSE Pharma announced that they have entered into a collaboration agreement to conduct the upcoming Tedopi® Phase III pivotal trial in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients who have failed on previous therapy. Simbec-Orion will manage this multi-centre, multi-country study involving up to 70 sites and 500 patients in the United States and Europe. Simbec-Orion has started the feasibility study for the planned study with international clinical experts and patient enrolment is planned for the second half of 2015. Simbec-Orion will be responsible for site selection, patient enrolment, clinical monitoring, data management, statistical analysis and regulatory affairs.
• • On June 23, 2014, OSE Pharma announced that it has received positive feedback from an End of phase 2 / Pre-­Phase 3 meeting with the FDA and Scientific Advice from the European Medicines Agency’s (EMA). OSE Pharma plans to initiate early 2015 a Phase 3 trial with OSE-­2101. The pivotal Phase 3 trial with OSE-­2101 will be conducted in patients with advanced stage IIIb invasive or metastatic stage IV NSCLC patients who express the HLA-­A2 receptor (45% of the NSCLC population).
• An US Phase 2 multicenter study with OSE-­2101 showed that the therapeutic cancer vaccine was effective increasing the specific T cytotoxic response and the survival while being well tolerated. Median survival for the OSE-­2101 treated patients in this Phase 2 study was 17.3 months compared to 12.0 months for patients in the HLA-­A2-­negative observation group. Of the patients treated with OSE-­2101, 91% elicited positive immune cytotoxic T cell response to one or more epitopes. The length of survival of patients treated with OSE-­2101 was correlated significantly with the breadth of the individual patient’s immune response (p<0.001) This study recruited a total of 135 NSCLC patients, 64 HLA-­A2 positive dosed with OSE-­2101 and 71 HLA-­A2 negative which formed the concurrent observation control group (providing information on survival at one year). All of the patients had advanced disease (invasive stage IIIb or metastatic stage IV) and were metastatic for 67% of them. The patients were previously highly treated with 65.5% of patients having received more than 2 previous lines).

Is general: Yes