Transgene Reports First Promising Efficacy Results with TG4001 in Combination with Avelumab in HPV-Positive Cancer at ESMO 2019
- Three of six patients showed durable responses (patients treated with the recommended Phase 2 dose)1
- Combination therapy results in changes in tumor microenvironment shifting immune status from “cold” to “hot”
- Clinical trial conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer
Conference call scheduled on October 3, 2019 at 2:30 p.m. CET
Strasbourg, France, September 30, 2019, 5:45 p.m. CET – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, today presented promising safety and efficacy data of TG4001 in combination with avelumab (BAVENCIO®), a human anti-programmed death ligand (PD-L1) antibody, in HPV-16+ recurrent or metastatic malignancies (including oropharyngeal cancers). These Phase 1b data have been presented in a poster (#1210P) at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain. TG4001 is a therapeutic vaccine based on a Vaccinia vector (MVA), which is engineered to express HPV-16 antigens (E6 & E7). It has been administered to more than 300 individuals in previous trials, demonstrating good safety, significant HPV clearance rate and promising efficacy results.
In the Phase 1b part of the trial, 9 heavily pretreated patients received either one of the two tested doses of TG4001 combined with a fixed dose of avelumab. The Phase 2 part of the trial started in October 2018 and will enroll 40 patients.
Key results of the Phase 1b trial are:
- 3 of the 6 patients treated with the higher dose of TG4001 showed durable partial responses1.
- No dose-limiting toxicity was observed, confirming a good safety profile of the combined regimen.
- T cell responses against the HPV-16 E6 and E7 antigens were detected in patients’ blood at day 43.
- The combination regimen was able to prime the immune system and modified positively the tumors microenvironment. Patients displayed increased immune cells infiltrates (including CD8 T cells) and an increased expression of genes associated with innate and adaptive immune response.
- An increase in PD-L1 expression in the tumor cells was seen.
Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene, commented, “These Phase 1b results with a combination treatment regimen containing TG4001 are promising. In this heavily pretreated population, the quality of the responses, in particular the duration of the responses, and the immune changes in the tumor, give us great confidence that we will see a positive outcome from the ongoing Phase 2 part of the trial. The results also confirm our conviction that a HPV-16 targeted therapeutic vaccine would be able to stimulate the immune response, and can advantageously be combined with an immune checkpoint inhibitor. Based on these results, I believe that the combination of TG4001 and an ICI could potentially offer a much-improved treatment option than single agent immune checkpoint inhibitor for patients with HPV-16+ recurrent or metastatic malignancies. Patient accrual in the Phase 2 part of the trial is in line with our expectations and the next clinical readout is expected in 1H 2020.”
Poster presentation - September 30, 2019, 12:00-13:00 - Poster Area Hall 4
Title: Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic HPV16 positive cancers (ID 2536)
Poster #1210P | Presenter: Christophe Le Tourneau (Institut Curie, Paris, France)
The abstract is available on the ESMO website.
The poster is available on Transgene’s website (Publication section) www.transgene.fr.
1These data compare favorably with current treatments in HPV-16 associated indications for patients with metastatic diseases receiving a second line of treatment. With immune checkpoint inhibitors, median overall survival remains inferior to 11 months and median progression free survival is between 2 and 4 months. In this heterogenous group of malignancies, overall response rates are around 10-15%.
About the trial
This multi-center, open-label trial is assessing the safety and tolerability, as well as the anti-tumor activity of this immunotherapy combination regimen (TG4001 + avelumab) in approximately 50 patients with HPV-16 positive cancers who had failed at least one line of systemic treatment for R/M 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 head and neck cancers, is the Principal Investigator of the study. The trial is 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).
In the Phase 1 part, 9 patients were enrolled to either one of the two doses of the vaccine (5x106 and 5x107 pfu). TG4001 was administered SC weekly for 6 weeks, every 2 weeks up to M6, and every 12 weeks thereafter. Avelumab was given IV at 10 mg/kg every 2 weeks. Tumor response was assessed by RECIST 1.1. For translational and immunological assessments, PBMC samples were collected longitudinally and tissue samples were collected at baseline and D43.
The Phase 2 part of the trial started in October 2018. 40 patients will be enrolled. They will receive the highest TG4001 dose tested in the Phase 1b part of the trial (5x107 pfu), in combination with avelumab at 10 mg/kg. The primary endpoint of the Phase 2 part is overall response rate. Secondary endpoints include progression free survival, overall survival, disease control rate and other immunological parameters. The interim readout is expected in 1H 2020.
More information on the trial is available on clinicaltrials.gov.
A conference call in English is scheduled on October 3, 2019, at 2:30 p.m. CET.
Webcast link to conference call:
Participant telephone numbers:
France: +33 (0) 1 7037 7166
United Kingdom: +44 (0) 20 3003 2666
United States: +1 212 999 6659
Confirmation code: Transgene
A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event.
- Mark Swallow