News in Cell and Gene Therapy for Rare Cancer Day 2025

According to the National Organization for Rare Disorders, more than 1 out of every 4 cancer diagnoses are for rare cancers and 25% of all deaths from cancer are attributed to rare cancers. Despite these numbers, funding for research for individual rare cancer types tends to be low and great unmet need remains for many patients with these diseases. That said, some cell therapy products have been approved or are under investigation for the treatment of certain rare cancers.

In honor of Rare Cancer Day, observed annually on September 30, CGTLive® is looking back at a collection of some of the news from the past few months focused on cell therapy for rare cancer, with an eye for offering a cross section of some of the progress being made in this field. Click the read more buttons for more details and information about each update.

LV20.19 CAR-T Produces 100% Overall Response Rate in Patients With R/R Mantle Cell Lymphoma

August 14, 2025 — Results from the phase 2 portion of a phase 1/2 trial (NCT04186520) published in the Journal of Clinical Oncology showed that the prespecified efficacy threshold for 90-day complete response (CR) rate was exceeded in patients with relapsed/refractory (r/r) mantle cell lymphoma (MCL) who were treated with an on-site manufactured, dual-targeted anti-CD20 and -CD19 chimeric antigen receptor T-cell (CAR-T) therapy (LV20.19).

At a fixed dose of 2.5 × 10⁶ cells/kg, treatment in the form of a single infusion of IL-7/IL-15–expanded LV20.19 CAR T-cells yielded a best overall response rate (ORR) of 100%, an 88% complete response rate, and a 12% partial response rate. Furthermore, disease relapse was recorded in only 2 patients at a median follow-up of 15.8 months. At this time point, the median progression-free survival and the median overall survival had not been reached.

With regard to safety, there were cases of cytokine release syndrome (CRS) reported in 94% of the patients. All cases were grade 1 or 2 in severity. In 18% of patients immune effector cell–associated neurotoxicity syndrome (ICANS) was reported, with 2 of the cases being deemed reversible grade 3 toxicities. There were 3 nonrelapse mortality events reported, with all having the context of ongoing B-cell aplasia.

FDA Gives Priority Review to BMS’s Supplemental BLA for Liso-Cel in R/R Marginal Zone Lymphoma

August 4, 2025 — Bristol Myers Squibb’s supplemental biologics license application (sBLA) for marketed autologous CD19-directed CAR T-cell therapy lisocabtagene maraleucel (liso-cel, marketed as Breyanzi) for marginal zone lymphoma (MZL) has been accepted by the FDA with priority review. The Prescription Drug User Fee Act goal date for the sBLA has been set for December 5, 2025.

Specifically, the sBLA is under review for adults with r/r MZL who have been treated with 2 or more previous lines of systemic therapy. The sBLA is supported by data from the phase 2 TRANSCEND FL clinical trial (NCT04245839).

“While initial therapy for MZL can be effective, multiple relapses over the course of several years are common, leaving patients in need of a new treatment option that can provide high, lasting response rates,” Rosanna Ricafort, the vice president and head of Late Development Program Leadership, Hematology and Cell Therapy, at BMS, said in a statement. “This FDA acceptance brings us one step closer to potentially standardizing CAR T-cell therapy as a treatment option for MZL, while building on our commitment to bring this personalized therapy to as many eligible patients as possible.”

European Commission Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia

July 24, 2025 — The European Commission (EC) has granted marketing authorization to obecabtagene autoleucel (Aucatzyl; Autolus), also known as obe-cel, a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of individuals 26 years or older with r/r B-cell precursor acute lymphoblastic leukemia (B-ALL).

The therapy was approved based on findings of the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which evaluated the therapy in adult patients with R/R B-ALL. Results from FELIX were published in the New England Journal of Medicine in November of last year and showed a complete response (CR) with incomplete hematological recovery (CRi) rate of 76.6% for patients in the pivotal cohort (n = 94) who were treated with obe-cel. Furthermore, it was reported that the median duration of response in the study for all patients who received obe-cel was 21.2 months and that the median event-free survival (EFS) was 11.9 months. The estimated 6-month EFS rate constituted 65.4%, and the estimated 12-month EFS rate was found to be 49.5%.

With regard to safety, cases of CRS occurred in 68.5% of patients (87 of 127). CRS cases assessed as grade 3 or higher occurred in 2.4% of patients (3 of 127). Cases of immune effector cell–associated neurotoxicity syndrome (ICANS) were reported in 22.8% of patients (29 of 127), and grade 3 or higher ICANS cases were reported in 7% of patients (9 of 127). The most common nonlaboratory adverse events assessed as grade 3 or higher included infections (unspecified pathogen infections occurred in 32% of patients), febrile neutropenia (24%), and bacterial infectious disorders (11%).

China's NMPA Accepts Satri-Cel NDA for Filing

July 7, 2025 — CARsgen's new drug application (NDA) for Claudin18.2-directed CAR-T satricabtagene autoleucel (satri-cel), which is intended to treat gastric/gastroesophageal junction adenocarcinoma (G/GEJA), has been accepted for review by China's National Medical Products Administration (NMPA) for Claudin18.2-positive advanced G/GEJA in patients who have received at least 2 prior lines of unsuccessful therapy.

“We are delighted to announce that the NDA for our self-developed Claudin18.2-targeted CAR T-cell product satri-cel has been accepted for review by China's NMPA,” Zonghai Li, MD, PhD, the founder, chairman of the board, CEO, and chief scientific officer of CARsgen, said in a statement. “This marks the world's first CAR T-cell therapy product for solid tumors to reach the NDA stage—a major milestone for the CAR-T field. I extend my sincere gratitude to all clinical investigators, trial coordinators, and patients involved in this program. We are hopeful for its timely approval to provide gastric cancer patients with a new treatment option.”

The NDA is supported primarily by data from the phase 2 CT041-ST-01 randomized controlled clinical trial (NCT04581473), which is being carried out in China. Notably, the company received priority review for satri-cel from the NMPA in May 2025 for the indication covered in the NDA and previously had received breakthrough therapy designation from the NMPA for it in March 2025. CARsgen has stated that it is also working to expand satri-cel's use to early-line and preioperative treatment via a phase 1b clinical trial (CT041-ST-05, NCT05911217) for it as an adjuvant treatment in pancreatic cancer and an investigator-initiated trial for it as a consolidation treatment after adjuvant therapy in G/GEJA that has been resected (CT041-CG4010, NCT06857786).

BrainChild Bio's Pediatric Brain Tumor CAR-T BCB-276 Reels in Breakthrough Therapy Designation

April 25, 2025 — BrainChild Bio's BCB-276, an investigational CAR-T therapy that targets B7-H3 and is being developed for the treatment of a type of pediatric brain tumor referred to as diffuse intrinsic pontine glioma (DIPG), has received breakthrough therapy designation from the FDA.

The FDA’s decision was supported by data indicating overall survival benefit for patients with brain tumors from the phase 1 BrainChild-03 clinical trial (NCT04185038), which is being carried out by Seattle Children’s, BrainChild’s academic partner. The company intends to conduct a pivotal phase 2 clinical trial for BCB-276 in order to support a biologics license application for the CAR-T product for children and young adults with DIPG. This study is expected to launch in the fourth quarter of this year. A Type B meeting held between BrainChild and the FDA in late 2024 brought the agency into alignment with the company regarding the plan for the trial.

“Breakthrough therapy designation gives us the possibility to accelerate the development path for BCB-276 as a CAR T-cell therapy that can potentially transform the treatment of DIPG,” Michael Jensen, MD, the founder and chief scientific officer of BrainChild Bio, said in a statement. “This designation is a major milestone for the children and families afflicted with these devastating brain tumors and represents a new paradigm for treating central nervous system brain tumors in children and adults, including a large number of patients suffering with glioblastomas and brain metastases.”

REFERENCES
1. Celebrate Rare Cancer Day with NORD. National Organization for Rare Disorders (NORD) website. Accessed September 30, 2025. https://rarediseases.org/get-involved/rare-cancer-day/