BT-001 is an oncolytic virus developed with Transgene’s Invir.IO™ platform, engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine.
The use of an oncolytic virus to deliver the anti-CTLA-4 locally and selectively in the tumor microenvironment allows high intratumoral concentrations, eliciting a stronger and more effective antitumor response. By reducing systemic exposure to a very low level, this local therapeutic activity furthermore allows to increase the safety and tolerability profile of the anti-CTLA-4 antibody.
Clinical phase 1/2a study ongoing
In September 2024, data were presented at the European Society of Medical Oncology (ESMO) Annual Meeting in Barcelona, Spain.
Key findings include:
- In the monotherapy part, in terms of overall response, stable disease was observed in 4/18 advanced solid tumor patients receiving BT-001 as single agent, while tumor shrinkage was observed in 2/20 injected lesions.
- In the combination part, two patients with partial responses were observed in a cohort of six heavily pretreated patients with advanced solid tumor receiving BT-001 in combination with pembrolizumab (one patient with a PD(L)-1 resistant melanoma and one patient with a leiomyosarcoma after five lines of therapy).
- BT-001 was well-tolerated with no dose-limiting toxicities (DLTs) observed. Two grade three adverse events related to BT-001 were reported (one skin ulcer and one lymphocyte count decrease). No DLTs were observed with repeated intratumoral injections of BT-001 alone (in 18 patients) or in combination with pembrolizumab (in 6 patients).
- Oncolytic virus BT-001 was shown to replicate and express its anti-CTLA-4 mAb payload in tumor tissue with rare and sporadic shedding, as shown by preliminary translational data.In May 2023, BioInvent and partner Transgene announced further positive progress and safety data in the ongoing Phase 1/2a trial evaluating BT-001 in patients with solid tumors, including melanoma.
A JITC (Journal of Immunotherapy of Cancer) paper titled ‘Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject “cold” tumors’ won the 2022 JITC Best Oncolytic and Local Immunotherapy Paper Award.
Study design
The overall objective of the Phase 1/2a study is to evaluate the safety and tolerability of BT-001 alone and in combination with pembrolizumab. The ongoing Phase 1 component of the study is divided into two parts: Part A will evaluate intra-tumoral injections of BT-001 as single agent in 18 patients with advanced solid tumor disease. The first two dose levels have been successfully completed, with 12 patients dosed. The highest dose cohort is currently enrolling patients. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab.
The subsequent Phase 2a component of the study 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.
Read more about the ongoing Phase 1/2a study
Evaluation of BT-001 alone and in combination with pembrolizumab
Out-licensing and partnering
In June 2022, BioInvent and Transgene announced a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ., USA, to evaluate the oncolytic virus BT-001 in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1/2a clinical trial for the treatment of patients with solid tumors. Under the terms of the supply agreement, will provide pembrolizumab to be used in combination with BT-001 in the ongoing Phase 1/2a clinical trial.
Since 2017, BioInvent and Transgene collaborate on the development of the drug candidate BT-001 which encodes both a differentiated and proprietary anti-CTLA-4 antibody and the GM-CSF cytokine. Transgene is contributing its proprietary oncolytic virus (OV) platform Invir.IO™, designed to directly and selectively destroy cancer cells by intracellular replication of the virus in the cancer cell (oncolysis). Oncolysis induces an immune response against tumors, while the “weaponized” virus allows the expression of genes carried by the viral genome, here an anti-CTLA-4 antibody, which will further boost immune response against the tumor.
The research and development costs as well as revenue and royalties are shared 50:50.