The first patient with refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) treated in the first cohort of the phase 1 clinical trial (NCT04690595) of PMB-CT01 (BAFFR-CAR T-cells) has reached complete remission (CR) at 1-month post treatment.1
"We are excited about the treatment outcomes as this patient had a relapsed B-cell ALL after prior treatment with chemotherapy and blinatumomab. His relapsed disease was both CD19- and CD22-negative, implying very limited available therapeutic options for him," principal investigator Ibrahim T. Aldoss, MD, associate professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, said in a statement.1
The patient experienced low grade treatment emergent toxicities, including grade 1 cytokine release syndrome (CRS) resolved without intervention, and no immune effector cell-associated neurotoxicity syndrome (ICANS). PMB-CT01 is a first-in-class BAFFR-targeted, autologous chimeric antigen receptor T-cell therapy. BAFF-R (B Cell Activating Factor Receptor) is a member of the tumor necrosis factor (TNF) receptor superfamily and is the main receptor for BAFF expressing almost exclusively on B cells. BAFFR-CAR T was constructed using anti-BAFF-R scFv (single-chain fragment variable) antibodies with CD3ζ and 4-1BB 2nd generation signaling domains.1
"He tolerated the treatment of BAFFR-CAR T Cells really well with only minimal and anticipated toxicities. Additionally, he achieved complete remission and clearance of minimal residual disease (MRD), indicating an excellent response to this effective therapy,” Aldoss added.1
The therapy was invented by the laboratory of Larry W. Kwak, MD, PhD, vice president and deputy director, City of Hope's Comprehensive Cancer Center. He is also PeproMene's scientific founder and compensated chair of its Scientific Advisory Board. City of Hope holds an interest in the investigational compound and PeproMene has licensed intellectual property related to the therapy. BAFFR-CAR T-cells have shown antitumor activity in lymphomas and leukemias in vitro as well as in animal models.
"PeproMene has achieved an exceptional milestone in the development and evaluation of PMB-CT01 with the observation of the acceptable safety profile and complete response in this PMB-CT01 treated B-ALL patient. These initial clinical outcomes are supported by City of Hope preclinical research data published in Science Translational Medicine in 2019, which shows BAFFR-CAR T Cells can effectively eliminate various B-cell malignancies including B-ALL and different subtypes of B-lymphomas," Hazel Cheng, PhD, chief operating officer, PeproMene, added.1
- PMB-CT01 demonstrated potential as a novel therapy for r/r B-ALL. The first patient in a phase 1 trial achieved complete remission.
- Treatment emergent toxicities were manageable, with only grade 1 cytokine release syndrome observed.
- Early clinical outcomes align with preclinical research, supporting PMB-CT01's efficacy and safety.
The CR follows promising preliminary data from the first 3 patients treated at dose level 1 of the phase 1, single-center, clinical trial for patients with non-Hodgkin lymphoma being conducted at City of Hope. The data were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, Californiam by principal investigator Elizabeth Budde, MD, PhD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope. PMB-CT01 was well-tolerated at dose level 1 and demonstrated potent anti-lymphoma activity with a 100% overall response rate (2 CR, 1 partial response) in patients with poor prognosis. CRS and ICANS cases were all grade 1 and reversible. Enrollment is ongoing at dose level 2.2
1. PeproMene Bio, Inc. Announces Complete Remission of the Cohort 1 First Patient Treated for Relapsed and Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) in the Phase 1 Clinical Trial of PMB-CT01 (BAFFR-CAR T Cells) at City of Hope. News release. PeproMene Bio. January 18, 2024. https://www.newswire.ca/news-releases/pepromene-bio-inc-announces-complete-remission-of-the-cohort-1-first-patient-treated-for-relapsed-and-refractory-b-cell-acute-lymphoblastic-leukemia-b-all-in-the-phase-1-clinical-trial-of-pmb-ct01-baffr-car-t-cells-at-city-of-hope-835314683.html
2. Budde LE, Del Real MM, Baird JH, et al. Promising Safety and Anti-Lymphoma Efficacy of Autologous Pmb-CT01 (BAFFRCAR T Cell) Therapy in a First-in-Human Phase 1 Study. Presented at: ASH 2023 Annual Meeting; December 9-12; San Diego, California. Abstract 221.