TG4001 HPV Cancer Vaccine Description
TG4001 is a therapeutic cancer vaccine candidate using an attenuated and modified poxvirus (MVA) as a vector expressing the HPV16 E6 and E7 proteins (rendered non-oncogenic) interleukin-2.
TG4001 is developed in Human Papillomavirus (HPV)-16 positive cancers, such as cervical, vaginal, and oropharyngeal squamous cell carcinoma of the head and neck.
On September 16, 2020, Transgene, previously known as Tipapkinogen Sovacivec, announced the analysis of the efficacy data from the Phase 1b/2 trial combining TG4001 with avelumab in HPV16-positive recurrent and/or metastatic malignancies showed promising clinical activity in the overall study population (34 evaluable patients).
Also, Transgene identified a selection criterion corresponding to patients showing particularly encouraging clinical activity. 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 or with immune checkpoint inhibitors in monotherapy. Responses are durable in most responder patients.
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 cancers. Key findings of the trial: The combination of TG4001 and avelumab demonstrates anti-tumor activity (23.5% ORR) in patients with previously treated recurrent and/or metastatic HPV-related cancers; the Presence of liver metastases has a profound impact on outcome in terms of ORR and PFS. In patients without liver metastases, an ORR of 34.8% and a median PFS of 5.6 months were achieved.
On March 10, 2021, Dr. Maud Brandely, Ph.D., Chief Medical Officer of Transgene, commented about this study: “I am pleased we have been able to use a methodologically sound trial design to move ahead with this randomized Phase II study quickly. The results from the initial Phase Ib/II study demonstrated the potential of the combination of TG4001 with an immune checkpoint inhibitor in this advanced disease setting. We observed encouraging clinical outcomes with a response rate reaching 34.8% and median progression-free survival of 5.6 months in patients without liver metastases. The observed median progression-free survival shows that this combination can induce a sustained and durable benefit, which may be based on the induction of a specific immune response. This study is expected to provide us with the data required to discuss the registration path of TG4001.”
Transgene is a France-based clinical-stage biotechnology company focused on designing and developing novel immunotherapeutics.
TG4001 HPV Cancer Vaccine Indication
TG4001 is indicated to treat Human Papillomavirus (HPV) 16+ recurrent or metastatic malignancies, including oropharyngeal cancers. Therapeutic vaccines are active and targeted immunotherapeutics. They induce a cascade of immune reactions that lead to the production of T cells that will only destroy specific malignant cells, says the company.
TG4001 HPV Cancer Vaccine Dosage
Dosing levels are being evaluated in ongoing clinical trials. TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens found in HPV16-related tumors and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2).
TG4001 HPV Cancer Vaccine News
March 10, 2021 - Transgene announced the initial Phase Ib/II trial conducted in France and Spain had been amended to include a randomized comparison of TG4001 with avelumab versus avelumab monotherapy in anogenital cancers. The submission of the amended protocol has been initiated in Europe. Also, Transgene received US FDA clearance of the protocol under TG4001 IND. Patient enrollment is expected to start in Q2 2021. The trial will focus on patients with recurrent or metastatic HPV16-positive anogenital cancer without liver metastases, including cervical, vulvar, vaginal, penile, and anal cancer.
October 27, 2020 - Transgene is communicating the content of the late-breaking poster abstract that will be presented at the SITC 35th Anniversary Annual Meeting (SITC 2020), to be held virtually November 9-14, 2020. The combination of TG4001 and avelumab demonstrates anti-tumor activity (23.5% ORR) in patients with previously treated recurrent and/or metastatic HPV-related cancers. The presence of liver metastases has a profound impact on outcomes in terms of ORR and PFS. In patients without liver metastases, an ORR of 34.8% and a median PFS of 5.6 months were achieved.
October 19, 2020 - Transgene announced that detailed results of the data from the Phase 1b/2 trial combining TG4001 would be presented in a poster presentation at the upcoming virtual meeting of the Society for Immunotherapy of Cancer taking place November 9-14, 2020.
July 22, 2020 - Transgene performed a pooled analysis of the data from the Phase 1b/2 trial combining TG4001. This analysis confirms that TG4001 can be safely combined with an immune checkpoint inhibitor and shows the clinical activity of this combination regimen. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer.
September 30, 2019 - Transgene 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.
April 4, 2019 - Study: Tipapkinogen Sovacivec therapeutic HPV vaccine's efficacy and safety in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up.
TG4001 HPV Cancer Vaccine Clinical Trials
Clinical Trial NCT03260023: Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers Including Oropharyngeal SCCHN (Recruiting)
The Phase 1b/2 study will consist of two parts: In the phase Ib part: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-patient dose escalation. In the phase II part, evaluation of efficacy and further evaluation of the safety of the combination of TG4001 and avelumab will be performed. In both parts, tumor response will be evaluated on local assessment using RECIST 1.1. All patients will be followed up until disease progression or death due to any cause or the date of data cut-off, whichever occurs first.
Clinical Trial NCT01022346: A Study of RO5217790 in Participants With High-Grade Cervical Intraepithelial Neoplasia (CIN) Associated With High-Risk Human Papillomavirus (HR-HPV) Infection (Completed)
This Phase 2 randomized, double-blind, placebo-controlled, parallel-arm study will assess the safety and efficacy of RO5217790 on the histologic resolution in participants with high-grade CIN associated with HR-HPV infection. Participants will be randomized to receive 3 subcutaneous injections of either placebo or RO5217790 on Days 1, 8, and 15. Study assessments will be made at Baseline, at Months 3 and 6, and every 6 months thereafter for an overall of 2.5 years.