The therapy is now being evaluated in a phase 2 study.
Novartis’ BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy PHE885 has shown efficacy in relapsed/refractory multiple myeloma (R/R MM).
Positive findings from a phase 1 study (NCT04318327) were presented at the European Hematology Association (EHA) 2022 Congress, June 9-12, held both virtually and in Vienna, Austria, by Adam S. Sperling, MD, PhD, Harvard Medical School and Dana-Farber Cancer Institute.
“BCMA-directed CAR T-cell therapies are approved for the treatment of R/R MM. However, prolonged product manufacturing times and a need for longer duration of response are major obstacles in this population, necessitating fast manufacture of a reliable and highly efficacious CAR T-cell product,” Sperling and colleagues wrote.
Out of 27 enrolled patients, 25 (93%) have successfully received PHE885 as of the data cutoff of April 20, 2022. These participants were dosed with 2.5x106 (n = 4; 16%), 5x106 (n = 13; 52%), 10x106 (n = 7; 28%), or 14.3x106 (n = 1; 4%) cells.
Investigators observed dose-limiting toxicities in 3 participants, these were asymptomatic grade 3 transaminitis at the highest dose level, asymptomatic grade 3 elevated pancreatic enzymes at the second dose level, and grade 4 neutropenia at the first dose level. All patients had at least 1 treatment-related adverse events (AEs) and experienced cytokine release syndrome (CRS). Two patients had grade 3 or higher CRS.
READ MORE: Dual-Targeted CAR T-Cell Therapy Continues to Show Efficacy in R/R Multiple Myeloma
All but 1 patient achieved a clinical response for a 93% objective response rate. Over half of patients (n = 15; 63%) had ongoing responses with a median follow-up of 6.4 months (1.1-15.5 months). There were 6 complete responses and 9 partial responses. Four patients died due to progressive disease.
“This phase 1 study is ongoing, and additional dose levels are being explored to identify an optimal recommended dose for expansion. PGHE994 expands rapidly in vivo, persists for prolonged periods, and demonstrates a stem cell memory phenotype,” Sperling and colleagues concluded.
PHE885 is developed with the use of Novartis' T-Charge platform that retains the naive/Tscm immunophenotype of the input leukapheresis, which could provide high rates of durable responses. The platform is also designed to reduce the manufacturing process time to less than 2 days, which could reduce the need for bridging therapy.
Also presented at the EHA 2022 Congress was an overview of the currently recruiting phase 2 trial (NCT05172596) assessing PHE885, which opened in February 2022. PHE885 will be infused either in the outpatient or inpatient in a single dose of 4×106 to 5×106 CAR T-cells. Patietns will be monitored for 24 months after infusion. Patients will then be followed up long term for up to 15 years.
The study is primarily assessing best overall response using International Myeloma Working Group criteria. Secondary endpoints include complete response rate, duration of response, progression-free survival, overall survival, rate and durability of minimal residual disease negativity, as well as safety and pharmacokinetics. Exploratory endpoints include assessment of CRS symptoms.