On December 6, 2020 CARsgen Therapeutics, a clinical-stage biopharmaceutical company, reported updated safety and efficacy results from its ongoing global clinical studies of CT053, an investigational chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) (Press release, Carsgen Therapeutics, DEC 6, 2020, View Source [SID1234572262]). The data were presented virtually in two oral sessions and one poster session at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) held December 5-8, 2020.

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CT053 is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of malignant plasma cells in multiple myeloma. CT053 notably uses a fully human anti-BCMA scFv domain, hypothesized to reduce immunogenicity and improve safety. The results for a total of 58 patients treated with CT053 CAR T cells in three studies were presented at the ASH (Free ASH Whitepaper) meeting.

Two years of follow-up data for 24 patients with RRMM in poor clinical condition who received CT053 in three parallel investigator-initiated studies were shown in the oral presentation given by Siguo Hao, MD PhD, from Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine.1 Data from these studies in China demonstrated an overall response rate (ORR) of 87.5%, with a median duration of response of 21.8 months, and median progression-free survival reached 18.8 months. The complete response/stringent complete response (CR/sCR) rate was 79.2% as defined by the International Myeloma Working Group Uniform Response Criteria for multiple myeloma. As of the June 30,2020 cutoff date, a total of 9 patients who had no evidence of myeloma in the bone marrow, known as minimal residual disease, continued to maintain CR/sCR. No grade 3 or higher cytokine release syndrome (CRS) events occurred, indicating the safety and tolerability of CT053 CAR T cells.

"We are encouraged by CT053’s remarkable duration of response given that response times to new multiple myeloma treatments generally shorten with each successive therapy. The treatment of CT053 was generally well tolerated in patients with refractory/relapsed multiple myeloma," shared Dr. Hao.

In the United States, 20 patients with RRMM have received CT053 in the ongoing Phase 1b single-arm, open, multicenter study (LUMMICAR STUDY 2).2 Shaji Kumar, MD, Professor of Medicine, Division of Hematology, Department of Internal Medicine, Mayo Clinic, gave the oral presentation reporting on these early data. As of the November 11, 2020 cutoff date, 20 heavily pretreated patients with RRMM [median 5 prior lines (range 3–11 lines); 25% extramedullary disease; 55% high-risk cytogenetics; 85% triple-refractory; 50% penta-refractory] received CT053: 14 patients received 1.5–1.8×108 cells and 6 patients received 2.5–3.0×108 cells. The patients tolerated treatment well with no grade 3 or higher CRS. No dose-limiting toxicities were observed, and the safety profile corresponded with that observed in the China studies. The first 18 patients who completed at least 8 weeks of efficacy follow-up experienced an ORR of 94% with a time to response of 1–3 months. Responses deepened after longer follow-up. The CAR T cells expanded well in vivo, and CAR copies were detected for at least 6 months.

"The CT053 data in the U.S. provide additional support that the fully human BCMA-specific scFv with fine-tuned binding affinity could be beneficial in managing patients with relapsed and refractory multiple myeloma," summarized Hong Ma, MD, Senior Vice President Clinical Development, CARsgen Therapeutics. "We have observed early and deep responses with CT053 in the study."

Wenming Chen, MD PhD, from Beijing Chaoyang Hospital, presented a poster reporting results from the ongoing a single-arm, open, multicenter Phase 1 clinical trial in China (LUMMICAR STUDY 1).3 As of the September 28, 2020 cutoff date, a total of 14 heavily pretreated patients with RRMM received CT053: 3 patients received 1.0×108 cells and 11 patients received 1.5×108 cells. The 14 patients tolerated treatment well. No dose-limiting toxicities occurred, no grade 3 or higher events of CRS or CRS-related encephalopathy were observed, and no anti-CT053 antibodies were detected. All 14 patients responded, resulting in an ORR of 100%.

"Our data showed that CT053 was well tolerated in patients with relapsed and refractory multiple myeloma and that significant and long-lasting responses were observed in patients despite heavy prior treatment," said Zonghai Li, Founder, President, CEO, and CSO of CARsgen Therapeutics. "The cells expanded well in vivo, and anti-CT053 immunogenicity was not detected. CT053 cells have the potential to be a breakthrough product for the treatment of relapsed and refractory multiple myeloma."

About CT053 and LUMMICAR
CT053 is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of malignant and normal plasma cells in the blood. The CT053 construct utilizes a fully human anti-BCMA scFv domain, hypothesized to reduce immunogenicity and improve safety. CT053 T cells are proposed to recognize, bind, and eradicate multiple myeloma cells that express BCMA.

CT053 has received regenerative medicine advanced therapy (RMAT) and orphan drug designations from the U.S. Food and Drug Administration and PRIority MEdicines (PRIME) and orphan drug designations from the European Medicines Agency.

CARsgen Therapeutics’ clinical development program for CT053 includes the clinical studies: LUMMICAR STUDY 1 (NCT03975907 Phase 1, China) and LUMMICAR STUDY 2 (NCT03915184 Phase 1b/2, United States and Canada). These are open-label, multicenter studies evaluating the safety and efficacy of CT053 in adult patients with RRMM. CT053 studies also include three investigator-initiated trials (NCT03380039; NCT03716856; NCT03302403 Phase 1, China). For more information, visit clinicaltrials.gov.

References:

Hao S, Jin J, Jiang S, et al. Two-year follow-up of investigator-initiated Phase 1 trials of the safety and efficacy of fully human anti-BCMA CAR T cells (CT053) in relapsed/refractory multiple myeloma. Blood. 2020;136(suppl 1):27–28. View Source
Kumar SK, Baz RC, Orlowski RZ, et al. Results from LUMMICAR–2: a Phase 1b/2 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in patients with relapsed and/or refractory multiple myeloma. Blood. 2020;136(suppl 1):28–29. View Source
Chen W, Fu C, Cai Z, et al. Results from LUMMICAR-1: a Phase 1 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in Chinese subjects with relapsed and/or refractory multiple myeloma. Blood. 2020;136(suppl 1):49–50. View Source