The oncology landscape continues to evolve rapidly in early 2025, marked by significant advancements in cell therapy and targeted treatments. Several key developments, ranging from regulatory decisions to innovative clinical trials, are shaping the future of cancer care.
Tabelecleucel Faces Manufacturing Hurdles
Atara Biotherapeutics received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for tabelecleucel (Ebvallo), an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy. This therapy is intended for patients with relapsed/refractory (r/r) EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). According to Atara Biotherapeutics, the CRL was not related to the clinical efficacy or safety data, but rather to issues identified during a standard pre-license inspection of a third-party manufacturer. Cokey Nguyen, PhD, CEO of Atara, stated that they are working with Pierre Fabre Laboratories, the FDA, and the manufacturer to resolve the issues and anticipate a potential approval within six months of resubmission.
EsoBiotec Initiates In Vivo CAR-T Trial
EsoBiotec has dosed the first patient in a phase 1 clinical trial in China for ESO-T01, an investigational BCMA-directed in vivo chimeric antigen receptor T-cell (CAR-T) therapy. This therapy is being evaluated for the treatment of r/r multiple myeloma (MM). EsoBiotec claims 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 leverages EsoBiotec’s ENaBL platform and Pregene Biopharma’s BCMA CAR-T transgene to reprogram patients’ T-cells within their bodies. Jean-Pierre Latere, PhD, CEO of EsoBiotec, noted that this approach could reduce treatment costs by an order of magnitude compared to ex vivo CAR-T therapy. The company anticipates sharing initial clinical data in the second half of 2025.
FDA Approves Obecabtagene Autoleucel for B-ALL
The FDA has approved obecabtagene autoleucel (Aucatzyl; Autolus Inc), known 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 approval was based on the phase 1b/2 FELIX clinical trial, which demonstrated overall complete remission (CR) rates above 60% and a median duration of remission beyond 12 months for those achieving complete remission within 3 months. The recommended dose is 410 × 106 CD19 CAR-positive viable T-cells, administered after lymphodepleting chemotherapy. Elias Jabbour, MD, lead investigator of the FELIX study, highlighted the unmet medical need in treating relapsed adult ALL and expressed hope for improved outcomes with obecabtagene autoleucel.
Arlocabtagene Autoleucel Shows Promise in Multiple Myeloma
Arlocabtagene autoleucel (arlo-cel, BMS-986393), a GPRC5D-targeted CAR T-cell therapy, has shown promising results in patients with heavily pretreated relapsed/refractory MM. Data from a phase 1 study presented at the 66th American Society of Hematology (ASH) Annual Meeting revealed a complete response (CR) rate of 48% at the recommended phase 2 dose (RP2D). The overall response rate (ORR) was 91% in patients who received the RP2D of 150x106 cells and had received three or more prior lines of treatment. Susan Bal, MD, lead investigator, noted the manageable safety profile and promising efficacy, with responses observed regardless of high-risk cytogenetics or prior BCMA-directed therapy.
Other Notable FDA Actions
- Revumenib (Revuforj) was approved for the treatment of adult and pediatric patients 1 year and older with relapsed or treatment-refractory acute leukemia that harbors a translocation involving the lysine methyltransferase 2A (KMT2A) gene.
- Zolbetuximab (Vyloy) was approved in combination with chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer whose tumors test positive for claudin 18.2 and negative for human epidermal growth factor receptor 2 (HER2).
- Zanidatamab (Ziihera) received accelerated approval to treat previously treated, unresectable or metastatic HER2-positive biliary tract cancer.
- Cosibelimab (Unloxcyt) was approved to treat metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) not eligible for curative surgery or radiation.
- Ensartinib (Ensacove) was approved to treat patients with ALK-positive locally advanced or metastatic NSCLC who have not yet been treated with an ALK inhibitor.
- Remestemcel-L (Ryoncil) was approved to treat children 2 months of age and older with acute GvHD that does not respond to steroids.
These developments highlight the ongoing innovation and progress in oncology, offering new hope and treatment options for patients with various types of cancer.
