Transgene, a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB (“BioInvent”), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, jointly announced positive progress and safety data of the ongoing Phase I/IIa trial evaluating BT-001 in patients with solid tumors, including melanoma.
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The initial data generated in Phase I part A demonstrated that BT-001 alone is well tolerated, with first signs of anti-tumor activity in a hard-to-treat population and confirmed the mechanism of action of BT‑001 as a single agent. The initial findings are as follows:
- After administration, the virus was found in the tumors after several days. This suggests that BT‑001 is able to persist and replicates within tumors;
- This finding is consistent with the expression of the anti-CTLA-4 observed in the tumor with no detectable systemic exposure;
- No spreading in blood or biological fluids has been detected, suggesting high tumor specificity;
- Tumor shrinkage was observed in one patient in the first cohort.
The part A of the Phase I trial aims to establish the tolerability of BT-001 and to determine the dose and administration schedule for further development. Repeated (every 3 weeks) and ascending doses of intratumoral administration of BT‑001, as a single agent, will be administered to up to 18 patients with metastatic/advanced tumors.
The first two dose levels have been successfully completed, with 12 patients dosed to date. The Safety Review Committee (SRC) has stated that the safety profile supports escalation to the highest dose level of Phase I part A.
The Phase I part B is planned to start in H2 2022. This part will assess the combination of intratumoral injections of BT-001 with intravenous administrations of the anti-PD1 antibody pembrolizumab.
BT-001 is based on Transgene’s patented oncolytic vector and is encoding BioInvent’s proprietary anti‑CTLA‑4 antibody; it is codeveloped by the two biotechnology companies.
The ongoing Phase I/IIa (NCT04725331) 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 receive single agent, intra-tumoral administrations of BT-001. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab. The Phase IIa will evaluate the combination regimen in several patient cohorts with different 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.