P1, N=50, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

P2, N=146, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2025 --> Feb 2025 | Trial primary completion date: Dec 2025 --> Feb 2025

Global sensitivity analysis highlighted relative antigen expression, maximum killing rate constant, and CAR-T expansion rate constant as major determinants for observed exposure of dual-targeted CAR-T-cell therapy. This modeling framework could facilitate dose-optimization and construct refinement for dual-targeted bicistronic CAR-T-cell therapies, serving as a valuable tool for both forward and reverse translation in drug development.

After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy...Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage...This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.

P1/2, N=80, Recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Mar 2026 --> Dec 2026

Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

"Background: Ciltacabtagene autoleucel (cilta-cel) demonstrated superior progression-free survival (PFS) and overall survival compared to standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOTs) in the phase 3 CARTITUDE-4 trial. The increase in the TTNT and sustained benefits in PROs, along with prolonged survival, support cilta-cel as a new SOC treatment for MM patients who are refractory to lenalidomide and have received 1-3 prior LOTs. Importantly, with ~3 years of follow-up, a single infusion of cilta-cel provided patients with a longer delay in worsening of MM related symptoms, functional impacts, and GHS/QoL. The totality of clinical and patient-reported evidence demonstrates the significant benefit of cilta-cel."

P1/2, N=118, Recruiting, Gracell Biotechnologies (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting

Our findings indicate that BCMA-targeting BATs offer a promising and accessible therapeutic strategy for MM, with a simple, rapid, and cost-effective production process. These results support future development of BITE-armed T cells as a novel cancer treatment to enhance therapeutic outcomes for MM patients.

P=N/A, N=200, Not yet recruiting, CARsgen Therapeutics Co., Ltd.

P2, N=20, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting

Single-cell analyses revealed increased clonality in the CD4+ and CD8+ T cell compartments in patients with previous exposure to BsAbs at leukapheresis and on day 30 after CAR-T infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM.

The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T therapy, demonstrated safety and clinical efficacy in patients with RRMM.

P1/2, N=75, Recruiting, Essen Biotech | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Jul 2024

P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2028 --> Feb 2027

P1, N=18, Not yet recruiting, Bioray Laboratories

P1, N=30, Not yet recruiting, Arcellx, Inc.

P1, N=12, Not yet recruiting, Washington University School of Medicine

P1, N=25, Terminated, Cartesian Therapeutics | Phase classification: P1/2 --> P1 | Active, not recruiting --> Terminated; Phase 1 enrollment completed. Further clinical development terminated.

P3, N=618, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

P3, N=743, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P1, N=30, Not yet recruiting, Medical College of Wisconsin | Trial completion date: May 2028 --> May 2029 | Trial primary completion date: May 2027 --> May 2028

P2, N=30, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

BsAb and CAR-T may overcome individual standard genomic RF, however harboring multiple genomic RF remains adverse. Clinically available extended genomic characterization predicts response better than FISH alone in this large cohort treated with BsAb/CAR-T. This work will extend into pre-/post-therapy whole genome sequencing for more granular data analysis.

In this review, we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy. These insights, combined with lessons learned from benchmarking CAR-T based products in recent clinical trials, aim to address the challenges posed by T cell exhaustion, potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.

EMD-specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long-term outcomes.

CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00).

P2, N=50, Not yet recruiting, Wake Forest University Health Sciences | Trial completion date: Aug 2027 --> Nov 2027 | Initiation date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2027 --> Nov 2027

P2, N=20, Not yet recruiting, PETHEMA Foundation

P3, N=450, Recruiting, Kite, A Gilead Company | Not yet recruiting --> Recruiting

In patients with recurrent and refractory multiple myeloma who underwent multiple cycles of chemotherapy and radiotherapy, dual-targeted CAR-T cell therapy aimed at BCMA and CS1 failed to effectively manage extramedullary relapse. Elevated expression of MYBL2 in multiple myeloma correlates with a poorer prognosis.

P2, N=30, Not yet recruiting, Janssen Research & Development, LLC

These results demonstrate that UCARTCS1 has potent anti-MM activity against MM cell lines and primary MM cells, as well as in an MM xenograft model and support the evaluation of UCARTCS1 in patients with advanced MM.

P1/2, N=118, Not yet recruiting, Gracell Biotechnologies (Shanghai) Co., Ltd.

Mechanistic studies reveal the involvement of both CAR and IL-2 receptor endodomains in the CAR-E mechanism of action. The CAR-E approach avoids the need for specific engineering and enables CAR T cell therapy with lower cell doses.

P1, N=18, Not yet recruiting, Zhejiang University | Trial completion date: Oct 2026 --> Oct 2027 | Initiation date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2026 --> Jun 2027

Our results suggest that CAR-T cell activation negatively influences hematopoietic differentiation through paracrine effects inducing HSPCs maturation arrest. Moreover, our study contributes to the understanding of severe cytopenia observed after CAR-T therapy in MM and provides potential treatments to prevent or decrease its severity.

P2, N=50, Not yet recruiting, Wake Forest University Health Sciences

P1, N=78, Completed, Juno Therapeutics, a Subsidiary of Celgene | Active, not recruiting --> Completed | N=150 --> 78 | Trial completion date: Jun 2025 --> Jul 2024 | Trial primary completion date: Jun 2025 --> Jul 2024

P1, N=9, Not yet recruiting, Wuhan Union Hospital, China

P1/2, N=49, Not yet recruiting, Omar Nadeem, MD

P1, N=21, Not yet recruiting, Novatim Immune Therapeutics (Zhejiang) Co., Ltd.