Top News in Oncology Cell Therapy for World Cancer Day 2025
For World Cancer Day, held annually on February 4, take a look at the stories that have stood out in oncology cell therapy in recent months.
World Cancer Day, observed annually on February 4 by the patient and clinician communities, is organized by the Union for International Cancer Control and intended to improve awareness, education, and action towards ending preventable deaths from cancer. The CGTLive® team regularly follows along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders, and cancer is one of the key therapeutic areas of interest in the field of cell therapy.
The news items below appeared among the top pieces on CGTLive's oncology page that our team produced in the past several months, whether because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in oncology cell therapy during the past few months.
Click the buttons to read further into these stories.
1. FDA Issues CRL for Atara Biotherapeutics’ BLA for T-Cell Immunotherapy Tabelecleucel for EBV+ PTLD
January 16, 2025 — The FDA has issued a complete response letter (CRL) to Atara Biotherapeutics regarding its biologics license application (BLA) for tabelecleucel (tab-cel, also known as Ebvallo), an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy, which is under evaluation for the treatment of patients with relapsed/refractory (r/r) EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD).
Notably, the CRL was related to issues with a standard prelicense inspection of a third-party manufacturer for tab-cel rather than to any concerns regarding the efficacy and safety data contained within the BLA. The manufacturing process itself was not implicated, and the FDA has not requested additional clinical trials for tab-cel.
“We are working closely with our partner Pierre Fabre Laboratories, the FDA, and the third-party manufacturer to address the feedback to support marketing approval for EBVALLO,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement. “Once the third-party manufacturer GMP compliance issues have been adequately addressed, we will file for a resubmission, which we would expect to be potentially approved within 6 months of resubmission. Atara and its partner Pierre Fabre remain confident in the potential of Ebvallo and are committed to bringing this potential first-in-class medicine to United States patients with EBV+ PTLD who have limited treatment options and significant unmet need.”
2. First Patient With Multiple Myeloma Dosed in EsoBiotec's Trial for In Vivo CAR-T ESO-T01
January 9, 2025 — The first patient has been dosed in an early phase 1 investigator-initiated clinical trial (NCT06691685) taking place in China for EsoBiotec's ESO-T01, an investigational BCMA-directed in vivo chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of r/r multiple myeloma (MM).
According to EsoBiotec, this is the first time a patient has been treated with an in vivo BCMA-directed CAR-T therapy in a clinical trial. ESO-T01 is intended to reprogram patients’ own T-cells within their body via the use of EsoBiotec’s ENaBL, a third-generation immune-shielded cell specific lentiviral vector platform, and their collaborator Pregene Biopharma’s BCMA CAR-T transgene. EsoBiotec states that their approach may be able to provide the treatment at a cost 1 order of magnitude lower than the cost of ex vivo CAR-T therapy.
“ESO-T01 has the potential to offer a simplified patient journey, with several benefits over current treatments for MM that are often costly and have unfavorable side effects,” EsoBiotec CEO Jean-Pierre Latere, PhD, said in a statement. “Our treatment does not require lymphodepletion, is immediately available to patients without any waiting time, and is administrated in a single intravenous dose that takes less than 10 minutes. This is why we value our collaboration with Pregene Biopharma to develop ESO-T01, as we share the common goal of making this groundbreaking treatment affordable and available to patients globally. We look forward to sharing initial clinical data in the second half of 2025.”
3. FDA Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia
November 8, 2024 — The FDA announced that has approved obecabtagene autoleucel (Aucatzyl; Autolus Inc), known colloquially as obe-cel, a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with r/r B-cell precursor acute lymphoblastic leukemia (ALL). The therapy was approved based on the findings of the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which showed rates of overall complete remission (CR) above 60% and a median duration of remission beyond 12 months for those who achieved complete remission within 3 months.
The agency's total recommended dose of obe-cel is 410 × 106 CD19 CAR-positive viable T-cells, preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy and administered as split-dose infusion on Day 1 and Day 10 (±2 days) of treatment, based on bone marrow blast assessment. No REMS was required by the FDA.
“Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes,” Elias Jabbour, MD, the lead investigator of the US-based portion of the FELIX study and a professor of Leukemia and ALL section chief at The University of Texas MD Anderson Cancer Center, said in a statement. “This milestone approval, based on the demonstrated clinical benefit of Aucatzyl, brings new hope for adult patients with r/r B-ALL.”
4. Verismo Therapeutics’ Trial for R/R B-NHL CAR-T SynKIR-310 Doses First Patient
January 14, 2025 — The first patient has been dosed in Verismo Therapeutics’ phase 1 CELESTIAL-301 clinical trial (NCT06544265), which is evaluating SynKIR-310, a CAR-T therapy based on the company's killer immunoglobulin-like receptor (KIR)-CAR platform, in patients with r/r B-cell nonHodgkin lymphoma (B-NHL).
The multicenter trial is open to patients with forms of r/r B-NHL including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Notably, the study is open to patients who have previously received another CAR-T therapy but whose disease relapsed or was refractory to the therapy, as well as patients who have never previously received a CAR-T product. The first patient’s dosing took place in Denver, Colorado at the Sarah Cannon Research Institute (SCRI) at Colorado Blood Cancer Institute (CBCI).
SynKIR-310 is based on Verismo’s KIR-CAR platform, which was developed at the University of Pennsylvania, and is intended to enable sustained antitumor activity of the CAR T-cells in difficult tumor microenvironments. KIR-CAR is a dual-chain CAR T-cell platform that uses a natural killer cell derived KIR and DAP12, which acts as a novel costimulatory molecule for T-cells, to improve expression and persistence. In preclinical models resistant to traditional CAR-T approaches it showed prolonged functional T-cell persistence and effected tumor regression.
5. Arlo-Cel Generates Excitement, Moves Quickly to Phase 3 Studies for Multiple Myeloma
December 9, 2024 — The GPRC5D-targeted CAR T-cell therapy arlocabtagene autoleucel (arlo-cel, BMS-986393) at the recommended phase 2 dose (RP2D) elicited a complete response (CR) rate of 48% for patients with heavily pretreated relapsed/refractory MM, according to extended follow-up from part A and B of cohort A in the phase 1 CC-95266-MM-001 study presented at the 66th American Society of Hematology (ASH) Annual Meeting, held December 7-10, 2024, in San Diego, California.
In 26 patients who received the RP2D of 150x106, the overall response rate (ORR) with arlo-cel was 91% for patients with MM who had received 3 or more prior lines of treatment. This response rate also included a very good partial response in 22% of patients. Across all doses examined, the median duration of response was 18.0 months (95% CI, 13.3-23.0). Responses were observed regardless of high-risk cytogenetics or prior treatment with a BCMA-directed targeted therapy. At the data cutoff following a median duration of follow-up of 16.1 months, 38% of responses were ongoing.
"Arlocabtagene autoleucel is a potential first in class GPRC5D-targeted autologous CAR T-cell therapy, which has been administered to patients with heavily pretreated MM showing manageable safety and promising efficacy," lead investigator Susan Bal, MD, University of Alabama at Birmingham, said during a presentation of the results. "There's promising preliminary efficacy with a high overall response rate. Notably, these responses and outcomes are not affected by exposure to prior therapies."
