Beyond Chemotherapy: Latest FDA Approvals Cement the Era of Targeted Cell and Molecular Therapies

The closing months of 2024 saw the U.S. Food and Drug Administration deliver a series of oncology approvals that collectively underscore a pivotal shift toward biomarker-driven, precision treatments for a range of malignancies. From redesigned cell therapies to innovative dual-action antibodies, the regulatory decisions signify a continued national commitment to moving beyond traditional cytotoxic methods in favor of highly specific molecular intervention.

The new approvals focused on identifying and disrupting previously unexploited weaknesses in cancer cells. For patients with relapsed or refractory acute leukemia carrying a specific genetic translocation known as KMT2A, a novel compound, revumenib (Revuforj), was granted approval. This drug represents a new class of agents known as menin inhibitors, which block a key protein interaction crucial for the survival of these particular leukemia cells.

In the treatment of upper gastrointestinal cancers, a new targeted path emerged. Zolbetuximab (Vyloy), an antibody, was approved for use alongside a common chemotherapy regimen in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer whose tumors display high levels of the protein claudin 18.2. This approval expands the number of molecular alterations that can be used to tailor a patient’s initial treatment strategy.

The regulatory landscape also broadened options for some of the most common cancers. For patients navigating hormone receptor-positive, HER2-negative metastatic breast cancer, the FDA approved inavolisib (Itovebi) in combination with two existing drugs, palbociclib and fulvestrant. The combination targets tumors that harbor a mutation in the PIK3CA gene, a frequent molecular change in this breast cancer subtype. Separately, for patients with ALK-positive non-small cell lung cancer, the second-generation ALK inhibitor, ensartinib (Ensacove), was approved for those not previously treated with an ALK inhibitor. This newer compound was specifically designed to be effective against tumor cells that have developed resistance to prior inhibitors, and to better penetrate the brain, where lung cancer often spreads.

Perhaps the most sophisticated molecular breakthroughs came in the form of bispecific antibodies, which are designed to hit two distinct targets simultaneously. Accelerated approval was granted to zanidatamab (Ziihera) for advanced biliary tract cancer with HER2 overexpression, marking it as the first bispecific antibody approved to target HER2 across any cancer type. Similarly, zenocutuzumab (Bizengri) was approved for advanced pancreatic and non-small cell lung cancers driven by the NRG1 gene fusion. This dual HER2/HER3-targeting antibody represents a much-needed therapeutic option for these rare and often challenging-to-treat tumors.

In the realm of cellular medicine, a new generation of immunotherapy was introduced. Obecabtagene autoleucel (Aucatzyl), a CD19-directed CAR T-cell therapy, received approval for adult and pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. While multiple CAR T-cell therapies are now approved for hematologic cancers, this particular design utilizes a unique antibody fragment to recognize the cancer cell’s target, a development that is theorized to potentially result in a reduction in some of the therapy's more severe immune-related side effects.

The cumulative effect of these approvals, all stemming from robust clinical data, is the refinement of oncology care into an increasingly individualized and biologically precise endeavor. Each decision reinforces the principle that identifying a tumor’s specific molecular drivers now dictates the choice of treatment more than its anatomical location alone.

Source:https://www.aacr.org/blog/2025/01/03/fda-approvals-in-oncology-october-december-2024/