Therapy Areas: Vaccines
Transgene Completes Safety and Tolerability Assessment of TG4001 in Combination with Avelumab in Phase 1b Part of Trial in HPV-Positive Cancer Patients
26 December 2018 - - The primary endpoint (safety and tolerability) was met in the Phase 1b part of a trial combining TG4001 and avelumab, a human anti-programmed death ligand (PD-L1) antibody, as a treatment for HPV-16+1 recurrent or metastatic malignancies, such as oropharyngeal squamous cell carcinoma of the head and neck (SCCHN), French biotechnology company Transgene (PAR: TNG) said.

In the Phase 1b part of the trial, 9 patients received escalating doses of TG4001 combined with a fixed dose of avelumab. No dose-limiting toxicity was observed, confirming a satisfactory tolerability profile for the combined regimen, allowing the trial to progress to the Phase 2 part.

The Phase 2 part of the trial will enroll 40 patients with HPV16+ recurrent or metastatic SCCHN. Patients will receive the highest TG4001 dose tested in the Phase 1b part of the trial, in combination with avelumab at 10 mg/kg, until disease progression.

The first patients have already been enrolled.

The first data from this trial on the activity of the combination are expected during the second half of 2019.

This multi-centre, open-label trial will assess the safety and tolerability, as well as the anti-tumor activity of this immunotherapy combination regimen (TG4001 + avelumab) in up to 50 patients (NCT03260023).

Prof. Christophe Le Tourneau, M.D., PhD, Head of the Department of Drug Development and Innovation 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).

TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated vaccinia vector, which is engineered to express HPV-16 antigens (E6 and E7) and an adjuvant.

It is designed to have a two-pronged antiviral approach: to alert the immune system specifically to HPV-16-infected cells that have started to undergo precancerous transformation (cells presenting the HPV-16 E6 and E7 antigens) and to further stimulate the infection-clearing activity of the immune system through interleukin 2.

TG4001 has been administered to more than 300 individuals, demonstrating good safety, significant HPV clearance rate and promising efficacy results. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors.

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions.

By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.

Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity in vitro3-5. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

The US Food and Drug Administration granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma and patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

These indications are approved under accelerated approval based on tumor response rate and duration of response.

Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
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