GC012F also showed efficacy in B-cell non-Hodgkin lymphoma.
Updated data from the phase 1, first-in-human study (NCT04236011) of Gracell Biotechnologies’ GC012F continues to demonstrate the CD19/BCMA dual-targeted chimeric antigen receptor (CAR) T-cell therapy’s efficacy in relapsed/refractory multiple myeloma (R/R MM).1
Results from the final dataset of 29 patients were presented at the European Hematology Association (EHA) 2022 Congress, June 9-12, held both virtually and in Vienna, Austria, by Juan Du, professor, Changzheng Hospital, Shanghai, China.
"The updated data of the final dataset of 29 treated patients underscore the deep responses achieved with GC012F, including a 100% minimal residual disease (MRD) negativity rate in all patients treated," Martina Sersch, MD, PhD, chief medical officer, Gracell, said in a statement.2 "GC012F for the treatment of RRMM continues to demonstrate a favorable safety profile and a promising median duration of response (DOR)... in mostly high risk, heavily pretreated patients, including those with extramedullary disease and those who were previously exposed to proteasome inhibitors, immunomodulatory drugs and anti-CD38 agents.”
The multicenter study has enrolled and treated 29 patients between October 2019 and January 2022 with 1x105 (DL1), 2x105 (DL2), or 3x105 (DL3) GC012F cells per kilogram.1 Patients had a median of 5 prior lines of therapy and most (n = 26) were categorized as high risk by mSMART 3.0 criteria. Median follow-up was 11 months (range, 4.9-34.5) and is continuing. All patients achieved MRD negativity and most (n = 22; 75.9%) achieved MRD-stringent complete responses. By dose level, DL1 had a response rate of 100 % (n = 2), DL2 had a response rate of 80% (N = 8), and DL3 had a response rate of 100% (n = 17). Median DOR was 15.7 months 95% CI, 7.6-33.1).
GC012F had a manageable safety profile, with some cases of low-grade cytokine release syndrome (CRS; n = 27) although there were 2 grade 3 CRS cases (7%). No cases of immune effector cell-associated neurotoxicity syndrome were observed. Final duration of response and best overall response are still being evaluated and patients continue to be monitored with some delays in follow-up due to COVID-19 related lockdowns in Shanghai.
GC012F is developed using Gracells’ FasTCAR-enabled dual-targeting CAR-T platform and simultaneously targets CD19 and BCMA to potentially improve efficacy and reduce relapse. The FDA granted orphan drug designation to the therapy in November 2021 for the treatment of MM. GC012F is also being evaluated in B-cell non-Hodgkin lymphoma (B-NHL) in another phase 1 study, data from which were presented at the EHA 2022 congress by Xinfeng Chen, adjunct professor, First Affiliated Hospital of Zhengzhou University, China.3
Three patients with B-NHL have been dosed with 3x105, 3.7x104, and 2x105 cells as of February 22, 2022. So far, investigators have observed a 100% complete response rate at 1 month in all patients. Two patients have maintained this CR for 3 months. All patients experienced at least grade 3 neutropenia. There was 1 case of grade 3 cytokine release syndrome (CRS) and 2 cases of grade 1 CRS. The study is continuing to enroll patients.
“In addition, we presented at EHA the first-in-human data of GC012F in B-NHL, a potential second indication. We look forward to continuing developing this lead asset and providing a new treatment option to the patients with high unmet needs,” Sersch added to the statement.2