Valérie Gabarre @valeriegabarre of @OSEIMMUNO discusses the ATALANTE-1 trial and the TEDOPaM study presented by OSE Immunotherapeutics at #ESMO19.
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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. Moving immune checkpoint inhibitors (ICI) in first-line setting in advanced NSCLC, new treatment strategies are needed for patients who progress on treatment with ICI. Tedopi® (OSE-2101) is a neoepitope vaccine restricted to HLA-A2 positive patients (∼45% of NSCLC) targeting five tumor-associated antigens expressed in lung cancer cells: ACE, HER2, MAGE2, MAGE3 and P53. In a phase II trial (Barve et al. JCO 2008), Tedopi® showed a median overall survival (OS) of 17.3 months with a manageable safety profile in pre-treated advanced NSCLC patients. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase III study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2 positive patients with advanced NSCLC after progression on ICI.
Trial design
Patients with advanced NSCLC (EGFR and ALK negative), progressive disease to platinum-based chemotherapy with sequential or concurrent ICI, HLA-A2 positivity (blood test), ECOG PS 0-1, treated and asymptomatic brain metastases allowed, are randomized 2:1 to receive 1"‰ml Tedopi® subcutaneously Q3W for 6 cycles, then Q8W for the remainder of the year and finally Q12W, or SoC treatment (docetaxel 75"‰mg/m2 Q3W or pemetrexed 500"‰mg/m2 Q3W). In both arms, treatment continues until progression, intolerable toxicity or consent withdrawal. Stratification criteria are histology, best response to first-line, line rank of ICI. Tumor assessment is performed every 6 weeks (RECIST 1.1). Primary endpoint is OS; Secondary endpoints are: Progression Free Survival, Objective Response Rate , Disease Control Rate , Duration of response, Quality of Life and safety. This is a superiority study with a hazard ratio of 0.7, two-sided alpha 5% and power 80%, after 278 events are observed. An independent analysis (1y-OS rate) is planned in the first 84 patients treated with Tedopi®. Last study review by the Data Monitoring Committee in June 18 suggested that the study continues as planned. Translational research will evaluate pharmacodynamic markers of efficacy baseline and after treatment initiation in this population of NSCLC patients who progressed after ICI treatment.
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A randomized phase II study of maintenance therapy with multiepitope vaccine tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM "“ PRODIGE 63 GERCOR study)
FOLFIRINOX (5FU, folinic acid [FA], irinotecan [Iri], oxaliplatin [Ox]) is a 1st-line standard in fit Pts with aPDAC. Anti-PD-(L)1 as single agents have failed in aPDAC and new combination immunotherapies are needed. Tedopi (OSE2101) is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts targeting 5 tumor-associated antigens (ACE, HER2, MAGE2, MAGE3, TP53) frequently expressed in PDAC. This study aims to assess the efficacy and safety of Tedopi alone and in combination with anti-PD-1 nivolumab or FOLFIRI as maintenance therapy in aPDAC Pts after FOLFIRINOX induction CT.
Trial design
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Arm A (reference): FOLFIRI (n"‰="‰52) |
IV; FA 400"‰mg/m2, Iri 180"‰mg/m2, 5FU bolus 400"‰mg/m2 + continuous 2400"‰mg/m2/46h |
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Arm B: Tedopi (n"‰="‰52) |
Subcutaneous injection on D1 Q3W/6 doses then Q8W until month 12 [M12] then Q12W up to M24 |
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Arm C: Tedopi + nivolumab (n"‰="‰52) |
Tedopi + nivolumab 360"‰mg IV on D1 Q3W/6 doses then 480"‰mg Q4W up to M24 |
In Arms B and C, reintroduction of FOLFIRI at disease progression or unacceptable toxicity. Primary endpoint: overall survival rate at M12. Secondary: progression-free survival (CT-scan Q8W), duration of disease control, safety, response rate, RECIST v1.1/iRECIST comparison, HRQoL, Q-TWiST. Interim analysis after inclusion of 20 Pts in each arm. Translational research on tumor tissue (initial FFPE biopsy and optional re-biopsy at inclusion): RNAseq (cancer and stroma), mutation burden, MMR status, immune infiltrates; and in blood (before and on-treatment): cytokine panel, PBMC phenotyping, vaccine-antigen specific T-cells, TCR repertoire, extracellular vesicles to explore biomarkers and pharmacodynamics effects of Tedopi ± nivolumab.