Avelumab Plus TG4001 Shows Promising Efficacy in HPV16-Positive Metastatic Cancers

Avelumab in combination with a novel HPV16-targeted vaccine, demonstrated clinical activity as treatment of patients with HPV16-positive recurrent and/or metastatic malignancies.

Avelumab (Bavencio) in combination with the HPV16-targeted vaccine, TG4001, has demonstrated clinical activity as treatment of patients with HPV16-positive recurrent and/or metastatic malignancies, confirming that the vaccine can be safely combined with an immune checkpoint inhibitor for this patient population, a phase 1b/2 clinical trial (NCT03260023) showed.1

The cancers investigated in the study included oropharyngeal, anal, cervical, or other HPV16-positive cancers. All patients had disease that had progressed after up to 3 lines of prior chemotherapy treatment.

A total of 34 patients were evaluable for response and of those patients, 50% had no disease progression at 12 weeks. This result exceeded the anticipated median progression-free survival (PFS) of just 8 weeks for this patient population, as observed with the currently available treatment regimens for HPV16-positive recurrent metastatic cancers.

“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,” Christophe Le Tourneau, MD, the principal investigator of the trial and head of the Department of Drug Development and Innovation, Curie Institute, said in a press release.

Although impressive, this survival result is consistent with data presented in 2019 at the European Society of Medical Oncology (ESMO) Annual Congress. In the phase 1b portion of the study (NCT03260023), 9 patients were treated and confirmed partial responses per RECIST v1.1 criteria were observed in 3 patients. Three out of 5 evaluable patients showed detectable peripheric responses against HPV E6 and E7 antigens following treatment with the avelumab/TG4001 combination. Overall, the small group of patients showed a trend toward decreased circulating T cells. In addition, an increase in CD8 infiltration and/or a decrease in the infiltrated T cells:CD8 ratio was observed in the tissue of 4 evaluable patients at day 43. A doubling in PD-L1–positive cells was also seen in patients who had low to moderate expression.1,2

The vaccine was administered at a dose level of 5x106 and 5x107 pfu subcutaneously on a weekly basis for up to 6 weeks. Patients received avelumab at a dose level of 10 mg/kg intravenously every 2 weeks. The combination did not lead to any dose-limiting toxicities or serious adverse events.

Like with the ESMO findings, durable responses were reported in patients in updated findings from the trial. Translational analyses are still ongoing for this study and the complete results will be presented at an upcoming scientific conference.1

The primary end point being explored in the study is objective response rate per RECIST v1.1 criteria and the secondary end points are PFS, overall survival, disease control rate, and other immunological parameters.

The study is open to patients with histologically or cytologically confirmed metastatic or refractory/recurrent HPV16-positive cancers who have an ECOG performance status of 0 or 1 and a life expectancy of at least 3 months. Patients are also required to have available tumor tissue for biopsy; measurable disease; and adequate hematological, hepatic, and renal function to join the study.

“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 Maud Brandely, MD, PhD, chief medical officer of Transgene.


1. Transgene reports results from clinical study of tg4001 in combination with avelumab in advanced hpv-positive cancers. News release. Trangene. July 22, 2020. Accessed July 23, 2020. https://bit.ly/3eXf0Jv

2. Le Tourneau C, Delord JP, Cassier P, et al. Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-161 cancers. Ann Oncol. 2019;30(suppl 5):1210P. doi:10.1093/annonc/mdz253