Transgene and BioInvent International AB announced that the first patient of the Phase I part B clinical trial evaluating the combination of BT-001 and MSD?s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) has been dosed. The Phase I Part B of the trial explores repeated intra-tumoral injections of BT-001 in combination with intravenous infusions of KEYTRUDA. Transgene and BioInvent plan to enroll a minimum of 12 patients with metastatic or advanced solid tumors, including melanoma.

In accordance with clinical trial and supply agreement, KEYTRUDA is being supplied by MSD (a tradename of Merck & Co. Inc., Rahway, NJ, USA). Trial endpoints include safety, evaluation of efficacy, and assessment of immune changes in the tumor microenvironment.

Transgene and BioInvent are co-developing BT-001, an oncolytic virus designed using Transgene?s Invir.IO® platform encoding BioInvent?s differentiated anti-CTLA-4 antibody and human GM-CSF cytokine to elicit a strong and effective anti-tumoral response. The drug is currently being evaluated against solid tumors in a Phase I/IIa clinical trial as a single agent and in combination with the PD-1 checkpoint inhibitor KEYTRUDA. The inclusion of the last patient in Part B of the study is expected in first half of 2024.

Previously reported Phase I data confirmed the mechanism of action of BT-001 as a single agent and demonstrated first signs of anti-tumoral activity. The ongoing Phase I/IIa (NCT: 04725331) study is a multicenter, open label, dose-escalation trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment). Patient inclusions are ongoing in Europe (France, Belgium) and the trial has been authorized in the US.

This Phase I is divided into two parts. In part A, patients with metastatic/advanced tumors received single agent, intra-tumoral administrations of BT-001. Part B is exploring intra-tumoral injections of BT-001 in combination with KEYTRUDA.

In this part, KEYTRUDA is being provided to the trial by MSD (a tradename of Merck & Co. Inc., Rahway, NJ, USA). The Phase IIa will evaluate the combination regimen in several patient cohorts with selected tumor types.

These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment. BT-001 is an oncolytic virus generated using Transgene?s Invir.IO® platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting recombinant human anti-CTLA-4 antibody generated by BioInvent?s proprietary n-CoDeR®/F.I.R.S.T? platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response.

Therefore, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody may be greatly improved. BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent.