Promising Data Announced for TG4001 Vaccine Candidate
A French biotech company presented promising safety and efficacy data of TG4001 in combination with avelumab (BAVENCIO®), a human anti-programmed death-ligand (PD-L1) antibody, in Human Papillomavirus (HPV) 16+ recurrent or metastatic malignancies, including oropharyngeal cancers.
TG4001 is a therapeutic vaccine based on a Vaccinia vector (MVA), which is engineered to express HPV-16 antigens (E6 & E7).
Key results of the Transgene TG4001 Phase 1b trial are as follows:
- 3 of the 6 patients treated with the higher dose of TG4001 showed durable partial responses,
- 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 increased expression of genes associated with innate and adaptive immune response,
- An increase in PD-L1 expression in the tumor cells was seen.
These Phase 1b data have been presented in a poster (#1210P) at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain, on September 30, 2019.
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.
Dr. Maud Brandely, MD, Ph.D., Chief Medical Officer of Transgene, commented in a press release, “These Phase 1b results with a combination treatment regimen containing TG4001 are promising. The results also confirm our conviction that an 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.”
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.
Prof. Christophe Le Tourneau, M.D., Ph.D., 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.
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HPV infection is the most commonly diagnosed sexually transmitted disease and has been etiologically linked with condyloma acuminatum, squamous intraepithelial lesions, and anogenital malignancy, including cervical, vaginal, vulval, penile, and anal carcinoma.
Many patients with oropharyngeal squamous cell carcinomas, particularly those arising in the base of the tongue and in the tonsillar region, do not have the traditional risk factors associated with head and neck cancers, says UpToDate.
Epidemiologic and molecular studies have identified the HPV-16 genotype of HPV as a causative agent in many of these patients.
Other high-risk HPV genotypes, such as HPV-18, 31, or 33, are also causative but are less common.
The clinical 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.
Transgene is a biotechnology company that designs and develops innovative immunotherapies in clinical and preclinical applications.
HPV Cancer Vaccines are Published by Precision Vaccinations
- Transgene Reports Promising Early Efficacy Data for TG4001 in Combination With Avelumab in HPV-positive ESMO 2019 Cancers
- Transgene Press Releases
- Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers Including Oropharyngeal SCCHN
- Transgene Portfolio of Products
- HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma