On July 22, 2020 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that performed a pooled analysis of the data from the Phase 1b/2 trial combining TG4001, a HPV16 targeted therapeutic vaccine, with avelumab (BAVENCIO), a human anti-PD-L1 antibody, in HPV16-positive recurrent and/or metastatic malignancies (Press release, Transgene, JUL 22, 2020, View Source [SID1234562252]). This analysis confirms that TG4001 can be safely combined with an immune checkpoint inhibitor and shows clinical activity of this combination regimen. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer.
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The purpose of this exploratory Phase 1b/2 trial was to evaluate the safety and efficacy of the combination of TG4001 and an immune checkpoint inhibitor in a heterogeneous group of patients with aggressive, recurrent and/or metastatic HPV16-positive cancer. Clinical activity was observed in the overall study population (34 evaluable patients with oropharyngeal, anal, cervical, or other HPV16-positive cancers). In addition, Transgene has identified a selection criterion corresponding to patients showing particularly promising clinical activity in this trial. For more than 50% of these patients, the disease had not progressed at 12 weeks, compared to an expected median progression-free survival (PFS) of 8 weeks for this population with current treatment regimens [*].
Consistent with data presented at ESMO (Free ESMO Whitepaper) 2019 [1], durable responses have been observed in most of the responder patients. Transgene is currently completing translational analyses. Patient follow-up is still ongoing. Complete data will be presented at an upcoming scientific conference.
Transgene has stopped the trial in its current design. The Company intends to continue the clinical development of TG4001 in a larger, controlled confirmatory study.
All patients enrolled in the trial had an aggressive, recurrent and/or metastatic HPV16+ cancer that had progressed after one to three lines of chemotherapy. As previously reported [1], no new safety signals were observed.
Commenting on this novel immunotherapy regimen, Prof. Christophe Le Tourneau, MD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, and Principal Investigator of the trial, added: "The first results from this exploratory Phase 1b/2 trial are clearly encouraging. I believe that the response rate and the clinical outcomes of the combination compare favorably with existing standards of care and the historical data reported with immune checkpoint inhibitors alone."
"Patients with HPV16-induced cancers still do not have access to approved treatments designed to address the viral origin of their disease. We believe these data establish the clinical proof-of-concept of combining TG4001 with an immune checkpoint inhibitor. Based on these promising findings, Transgene intends to continue the clinical development of TG4001 in a larger, controlled confirmatory study and provide a better treatment option to this patient population," added Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.
About the trial
This multi-center, open-label trial is assessing the safety and efficacy of this immunotherapy combination regimen (TG4001 + avelumab) in patients with HPV16 positive cancers who have disease progression on at least one line of systemic treatment for recurrent/metastatic disease (NCT03260023). Prof. Christophe Le Tourneau, M.D., PhD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, and a world expert in drug development and head and neck cancers, is the Principal Investigator of the study. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, a leading science and technology company which in the US and Canada operates its biopharmaceutical business as EMD Serono, and Pfizer Inc (NYSE: PFE).
Patients received TG4001 at the dose of 5×107 pfu, SC, weekly for 6 weeks, every 2 weeks up to M6, and every 12 weeks thereafter, in combination with avelumab at 10 mg/kg, IV every two weeks, until disease progression.
The primary endpoint of the Phase 2 part is the overall response rate (ORR, using RECIST 1.1). Secondary endpoints include progression-free survival, overall survival, disease control rate and other immunological parameters.