Carteyva (relmacabtagene autoleucel)

Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

P2, N=10, Active, not recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2024 --> Oct 2024

P2, N=12, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=16, Recruiting, Ruijin Hospital | Not yet recruiting --> Recruiting

P2, N=12, Not yet recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P1, N=6, Recruiting, Liangjing Lu | Not yet recruiting --> Recruiting

Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints...These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.

P1, N=6, Not yet recruiting, Liangjing Lu

P2, N=10, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Trial primary completion date: Dec 2023 --> Apr 2024

P1, N=24, Not yet recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P2, N=10, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P1, N=0, Withdrawn, Shanghai Ming Ju Biotechnology Co., Ltd. | N=12 --> 0 | Not yet recruiting --> Withdrawn

P2, N=59, Active, not recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Aug 2028 | Trial primary completion date: Jun 2023 --> Oct 2023

P2, N=82, Active, not recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Recruiting --> Active, not recruiting

P1, N=12, Completed, Shanghai Ming Ju Biotechnology Co., Ltd. | Recruiting --> Completed

P=N/A, N=150, Not yet recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P=N/A, N=200, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P2, N=46, Not yet recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P2, N=20, Recruiting, Peking University Cancer Hospital & Institute | Not yet recruiting --> Recruiting

Our results demonstrated that CAR-T treatments are not cost effective in any-line settings for DLBCL patients at the WHO-recommended willingness-to-pay threshold (CNY257,241 per QALY) in the base-case analysis. Price reduction of CAR-T therapies is the main approach for lowering ICERs and ensuring that the drug costs are proportional to patient health benefits.

Compared with salvage chemotherapy, treatment with relma-cel for r/r LBCL in patients who have failed at least 2 lines of systemic therapy is within the cost-effective range from the perspective of Chinese healthcare system and represents a good use of healthcare resources.

P4, N=13, Not yet recruiting, Changhai Hospital

P4, N=8, Recruiting, Ruijin Hospital

The updated data of the RELIANCE study demonstrate durable response with and manageable safety profile of relma-cel in patients with heavily pre-treated r/r LBCL.

Patients with confirmed MCL, relapsed or refractory after at least 2 lines of therapy including anti-CD20 antibody, anthracycline or bendamustine, and BTKi were enrolled...Three participants (27.3%) underwent bridging therapy, Platinum or Cytarabine or combination (Table 1)... In this phase II study in China, the preliminary data of relma-cel provided promising clinical efficacy outcome (best ORR 81.8%, best CRR 54.5%) in high risk patients with r/r MCL and a low incidence of grade ≥3 CRS and ICANS. This study is ongoing and further results will be presented.

P2, N=20, Not yet recruiting, Peking University Cancer Hospital & Institute

P1/2, N=120, Recruiting, Chinese PLA General Hospital | N=80 --> 120

P1/2, N=80, Recruiting, Chinese PLA General Hospital

P1, N=12, Not yet recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

Materials & Methods Fifty-nine adults (age ≥18 years) with heavily pretreated (≥2 prior therapies), measurable and histologically confirmed r/r LBCL were randomized to receive lymphodepletion chemotherapy (LDC: fludarabine 25 mg/m 2 + cyclophosphamide 250 mg/m 2 daily×3) followed by a single infusion of autologous CAR+ T cells at a dose of 100×10 6 or 150×10 6 . Based on these data, relma-cel is undergoing approval in China. Figure : Kaplan–Meier estimates of (A) PFS and (B) OS by 3-month tumor response PR, partial response

P1, N=12, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

P2, N=82, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd. | Trial completion date: Jan 2022 --> Sep 2024 | Trial primary completion date: Apr 2020 --> Dec 2022

P2, N=59, Recruiting, Shanghai Ming Ju Biotechnology Co., Ltd.

Relma-cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR-T-associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China.

Patients were randomized to receive either 100×106 (low dose) or 150×106 (high dose) CAR+ T cells as a single infusion following fludarabine 25 mg/m2 & cyclophosphamide 250 mg/m2 daily×3 as lymphodepletion...The rates of CRS, neurotoxicity (NT), death, and the use of tocilizumab/steroids are shown in Table 1...The RELIANCE Trial provided the first demonstration of licensure-quality CAR-T manufacturing and clinical trial data generation in r/r patients originating in China. These results with relma-cel demonstrate similar preliminary response rates and PK profiles while providing the potential for an improved toxicity profile in heavily-pre-treated patients with r/r DLBCL having poor risk features relative to other CD19-specific CAR-Ts approved in the US and EU.

CD4 and CD8 subpopulation of CAR+ T cells were detected by cetuximab targeting EGFRt as a marker co-expressed with CAR transgene in fresh peripheral blood. Preliminary data from JWCAR029 Phase I study has demonstrated that pts with best response of CR/PR at 6 months had a relatively higher CAR T cell expansion. Current data suggested that the prevalence of pre-existing ATA may compromise CAR+T PK profile. No association of the presence or boost of ATA with efficacy or safety of JWCAR029 was observed.