TG4001 Therapeutic Vaccine Plus Avelumab Shows Promise in HPV-Positive Malignancies: Presented at ESMO Immuno-Oncology

By Jenny Powers

LUGANO, Switzerland -- December 15, 2020 -- Combining the therapeutic vaccine, TG4001, with avelumab remodels the tumour microenvironment (TME) and drives antitumour responses in human papillomavirus (HPV)-positive malignancies, according to a study presented at the Virtual 2020 European Society of Medical Oncology (ESMO) Immuno-Oncology Congress.

At 12 weeks, treatment with TG4001plus avelumab resulted in strong T-cell activity that drove the response. One (2.9%) of the 34 vaccinated patients achieved a complete response and 7 (20.6%) patients showed partial responses, yielding an objective response rate (ORR) of 23.5% and a disease control rate (DCR) of 41.2%.

Among the 23 patients without liver metastasis, the ORR was 57.3% and the DCR was 56.6%. Among the 5 patients with vulvar/vaginal cancer, the ORR was 40% (3 patients in this group did not have liver metastasis and their ORR rate was 66.7%).

The TG4001 vaccine expresses HPV-16 E6 and E7 proteins is based on a recombinant Modified Vaccinia Ankara vaccine, explained Christophe Le Tourneau, Institut Curie, Paris, France.

“The immune rejection of tumours is contingent upon the development of a specific immune response and presence of a favourable TME,” he said. “[This] treatment is associated with changes in the TME such as increase in immune infiltrate and expression of genes associated with activation of the immune system that drives an antitumour response.”

The phase II study (NCT03260023) enrolled 34 patients with various recurrent/metastatic HPV positive cancers, including HPV16-positive anal cancer (n = 15), oropharyngeal cancer (n = 8), cervical cancer (n = 6), and vulvar/vaginal cancer (n = 5). Most patients had received prior lines of chemotherapy for recurrent and/or metastatic disease.

All patients received TG4001 each week for 6 weeks, then every 2 weeks for 6 months and every 12 weeks thereafter, in addition to avelumab at 10 mg/kg every 2 weeks starting 1 week after the first vaccine dose.

Tissue and peripheral blood mononuclear cell (PBMC) samples were collected at baseline and on study day 43. Measurement of the T-cell response to HPV antigens was done using ex-vivo IFNgamma-ELI SPOT on PBMCs.

Seven of the 11 patients evaluable for ELISPOT had developed reactive T cells against E6, E7 or both antigens after vaccination.

Responders also showed higher median CD3 cell and CD8 cell infiltrates versus nonresponders. The infiltrates tended to increase during treatment and were accompanied by strong changes of the tumour transcriptomic profile by day 43. This profile demonstrated increased expression of effector T cell activation cascades.

“The combination of TG4001 vaccination and avelumab demonstrated a clinically relevant anti-tumour activity in patients with HPV-16 positive cancers having received multiple previous lines of treatment,” said Le Tourneau. “These results warrant further confirmation in a larger randomised clinical trial.”

Funding for this study was provided by Transgene and Merck Serono.

[Presentation title: TG4001 Therapeutic Vaccination Combined With PD-L1 Blocker Avelumab Remodels the Tumor Microenvironment (TME) and Drives Antitumor Responses in Human Papillomavirus (HPV)+ Malignancies. Abstract 63MO]

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