FDA Clears Biosyngen’s CAR-T Therapy BRG01 for Pivotal Trial in EBV-Positive Nasopharyngeal Carcinoma

Biosyngen’s chimeric antigen receptor T-cell (CAR-T) therapy BRG01 has been cleared by the FDA for a pivotal phase 2 clinical trial in patients with Epstein-Barr virus (EBV)-positive relapsed/metastatic nasopharyngeal carcinoma.¹

The FDA’s decision follows the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) move in July 2024 to clear the company for a phase 2 pivotal clinical trial for BRG01 in China.² As such, according to Biosyngen, BRG01 is the first cell therapy to move into a phase 2 clinical trial for relapsed/metastatic EBV-positive nasopharyngeal carcinoma in both the US and China.¹

"The approval of the phase 2 clinical trial for BRG01 is a testament to the robust preclinical data and strong early clinical results observed with this innovative therapy" Zhang Li, MD, MSc, the director of the Phase I Ward at the Sun Yat-Sen University Cancer Center and Deputy Director of the Lung Cancer Research Institute at Sun Yat-sen University, and principal investigator for the BRG01 clinical trial, said in a July 2024 statement, with regard to the trial’s clearance by the NMPA.¹ "BRG01 has the potential to be a first-in-class T-cell therapy for EBV-positive tumors, and we are confident in its ability to deliver meaningful clinical benefits to patients with this difficult-to-treat malignancy.”

Patients with advanced nasopharyngeal carcinoma have previously been treated with BRG01, which is engineered to target the EBV antigen commonly found on nasopharyngeal carcinoma tumor cells, in the context of a phase 1 clinical trial (NCT05864924) in the US and China.² The phase 1 study completed dosing of 9 patients with the disease who had previously been treated with 1 or more immune checkpoint inhibitors and for whom standard of care treatment was not successful. In terms of safety, it was noted that there were no dose-limiting toxicities and that BRG01 was well-tolerated. Furthermore, Biosyngen stated that at higher doses of the cell therapy, patients experienced more efficient disease control and greater reductions in tumor size. On PET-CT scans, necrosis and metabolic reduction of tumor lesions were seen in 75% of the patients treated at the high dose.

The FDA previously granted orphan drug designation to BRG01 on June 6, 2023, and fast track designation on July 10, 2023.^3,4 Investigational new drug (IND) application clearance for the phase 1 trial was obtained from the FDA in February 2023 and the phase 1 trial in China was cleared earlier by the NMPA’s CDE in December 2022. Biosyngen is also evaluating BRG01 for the treatment of EBV-positive lymphoma, with clearance for currently ongoing phase 1 trials having been secured from the FDA and CDE in April 2023.

Biosyngen is not the only company targeting EBV-associated conditions with cell therapy.⁵ Atara Biotherapeutics’ tabelecleucel (tab-cel) is an allogeneic EBV-specific T-cell immunotherapy that has been approved in the European Union under the name Ebvallo, but remains under investigation in the US for the treatment of EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD).^5,6 In January 2024, Atara reported data from an expanded population of patients with EBV+ PTLD with central nervous system involvement (CNS EBV+ PTLD) in the phase 2 EBVision trial (NCT04554914), which is also continuing to enroll patients with EBV+ immunodeficiency-associated lymphoproliferative diseases.⁷ In 18 patients with CNS EBV+ PTLD, including 1 patient with no prior treatment who achieved a complete response, the overall response rate was 77.8%.

“We are encouraged by our latest pivotal study data for tab-cel supporting our plan to file a BLA in Q2 2024, while our global commercial partner Pierre Fabre is starting to prepare the US launch,” Pascal Touchon, President and Chief Executive Officer, Atara, said in a statement.⁷

REFERENCES
1. Biosyngen’s BRG01 receives FDA approval for phase II clinical trial. News release. Biosyngen. August 12, 2024. Accessed August 13, 2024. https://www.biosyngen.com/index.php/Classification/38.html
2. Biosyngen’s BRG01 enters phase II clinical trial, A first-in-kind autologous EBV-specific CAR-T therapy for solid tumors on recurrent/metastatic nasopharyngeal carcinoma. News release. Biosyngen. July 16, 2024. Accessed August 13, 2024. https://firstwordpharma.com/story/5876299
3. Biosyngen’s first-in-class cell therapy BRG01 receives FDA Fast Track designation. News release. Biosyngen. July 10, 2023. Accessed August 13, 2024. https://www.biosyngen.com/index.php?m=home&c=View&a=index&aid=107
4. Biosyngen's Cell Therapy BRG01 Granted Orphan Drug Designation by the U.S. FDA for Treatment of Nasopharyngeal Cancer. News release. Biosyngen. June 6, 2023. Accessed August 13, 2024. https://www.asiaone.com/business/biosyngens-cell-therapy-brg01-granted-orphan-drug-designation-us-fda-treatment
5. Beitinjaneh A, Baiocchi R, Chaganti S, et al. New and updated results from a multicenter, open-label, global phase 3 (P3) study of tabelecleucel (tab-cel) for Epstein–Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) following allogeneic hematopoietic cell (HCT) or solid organ transplant (SOT) after failure of rituximab (R) or rituximab and chemotherapy (R+CT) (ALLELE). Presented at: 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.February 15-19, 2023; Orlando, FL. Abstract 25
6. Ebvallo. European Medicines Agency. Website. Accessed August 13, 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/ebvallo
7. Atara Biotherapeutics to present recent progress and key upcoming milestones at the 42nd annual J. P. Morgan healthcare conference. News release. Atara Biotherapeutics. January 8, 2024. Accessed August 13, 2024. https://investors.atarabio.com/news-events/press-releases/detail/333/atara-biotherapeutics-to-present-positive-new-tab-cel