1024P - Initial clinical results of BT-001, an oncolytic virus expressing an anti-CTLA4 mAb, administered as single agent and in combination with pembrolizumab in patients with advanced solid tumors

Background

BT-001 is an oncolytic vaccinia virus with enhanced replication selectivity in tumor cells and recombinantly armed to express GM-CSF and an anti-CTLA-4 mAb. BT-001 has shown strong antitumor activity in various murine tumor models, including cold tumors, with enhanced activity when combined with an anti-PD-1 agent. BT-001.01 trial aims at evaluating safety, PK, and antitumor activity of intratumoral (IT) BT-001 alone and in combination with IV pembrolizumab in patients (pts) with advanced solid tumors.

Methods

Patients received IT injections of BT-001 Q3W as monotherapy at the dose of 10⁶, 10⁷ or 10⁸ pfu/mL or 10⁷ pfu/mL in combination with 200 mg of pembrolizumab Q3W. The overall tumor response was assessed using RECIST 1.1 and iRECIST. Viral shedding and anti-CTLA-4 levels were monitored in the blood and injected lesions.

Results

As of Apr 22, 2024, a total of 24 pts (13 melanoma, 5 sarcoma, 6 other tumors) received BT-001: 18 pts in monotherapy and 6 pts in combination with pembrolizumab (12M, 12F, median age = 57 years, median number of BT-001 injections = 4 – range, 2-12). No dose-limiting toxicities were observed. Most common treatment-related Aes were pyrexia (42%), chills (17%) and skin ulcer (17%). Two grade 3 BT-001-related Aes were reported (1 skin ulcer and 1 lymphocyte count decreased) in the monotherapy part only. BT-001 was quantifiable by qPCR in biopsy in 6/6 pts and plasma in 2/16 pts. Anti-CTLA-4 was detected by qPCR and/or IHC in biopsy of 4/6 pts and was undetectable in plasma. In the monotherapy part, BOR was SD in 4/18 pts, while shrinkage of the injected lesions was observed in 2 pts. In the combo part, 2/6 pts had confirmed PR, 1 pt with PD(L)-1 resistant melanoma and 1 pt with leiomyosarcoma after 5 lines of therapies. Patient response profiles and updated results will be presented.

Conclusions

IT BT-001 alone or in combination with IV pembrolizumab was well tolerated and is showing early signals of activity in PD(L)1 refractory tumors. Preliminary translational data suggest that BT-001 is replicating in the tumor and that transgenes are expressed. Study is currently ongoing to further evaluate safety and activity.

Clinical trial identification

NCT04725331.

Editorial acknowledgement

Legal entity responsible for the study

Transgene.

Funding

Transgene, BioInvent International AB.

Disclosure

S. Champiat: Financial Interests, Personal, Advisory Board: Access Trial, Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, BeiGene, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Harpoon therapeutics, Immunicom, Inc., Mariana Oncology, Mima Health, Nanobiotix, Nextcure, Oncovita, Pierre Fabre; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KgaA, MSD, Novartis, Roche, Servier, Takeda; Financial Interests, Personal, Principal Investigator: AbbVie, Amgen, Boehringer Ingelheim, Bolt Biotherapeutics, Centessa Pharmaceuticals, Cytovation, Eisai, GSK, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, MSD, Ose Immunotherapeutics, Pierre Fabre, Replimune, Roche, Sanofi Aventis; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Roche, Sotio. C. Lebbe: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre, Inflax; Financial Interests, Personal, Funding: Roche, Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Other, Honoraria, Speaker’s Bureau, Research funding: Roche; Other, Honoraria, Speaker’s bureau, Travel, Accommodation, Expenses, Research funding, Board: Bristol Myers Squibb; Other, Honoraria, Speaker’s bureau, Travel, Accommodation, Expenses, Board: Novartis, MSD; Other, Honoraria, Speaker’s bureau: Amgen; Other, Honoraria, Travel, Accommodation, Expenses, Board: Pierre Fabre; Other, Honoraria: Pfizer; Other, Honoraria: Incyte; Other, Travel, Accommodation, Expenses, Board: Sanofi; Other, Board: Avantis Medical Systems, Jazz Pharmaceuticals; Other, Participation on a Data Safety Monitoring Board or Advisory Board: InflaRx. J. Baurain: Financial Interests, Institutional, Invited Speaker, educational lecture: MSD; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Sanofi, GSK, Pierre Fabre, AstraZeneca. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. C. Spring-Giusti, N. Stojkowitz, M. Brandely, A. Sadoun: Financial Interests, Personal, Full or part-time Employment: Transgene. A. Ropenga, M. Semmrich, A. McAllister: Financial Interests, Personal, Full or part-time Employment: BioInvent International AB. M. Chisamore: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. P. Cassier: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Advisor: OSE Immunotherapeutics; Financial Interests, Institutional, Local PI: AbbVie, Blueprint, Boehringer Ingelheim, Bristol Myers Squibb, Exelixis, GSK, Incyte, Janssen, Loxo/Eli Lilly, Novartis, Roche, Taiho, Toray Industries; Financial Interests, Institutional, Coordinating PI: Amgen, Transgene; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. All other authors have declared no conflicts of interest.