The Targeted Pulse: FDA Decisions and Clinical Advancements

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw FDA decisions, learned about care-changing trial data, heard from expert clinicians in the field, and analyzed long-term results. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

FDA Approves Ziftomenib in NPM1-Mutant Acute Myeloid Leukemia

The FDA has granted approval to ziftomenib (Komzifti, formerly KO-539) for treating adult patients with relapsed or refractory acute myeloid leukemia harboring a mutant NPM1 gene. This makes ziftomenib the first approved Menin inhibitor for this specific, relapse-prone indication.

The approval is based on final data from the phase 2 KOMET-001 trial, where the drug achieved a cumulative complete remission (CR) or CR with partial hematological recovery rate of 23%, and an overall response rate of 33%. The median overall survival (OS) was 6.6 months. The oral agent was generally well-tolerated, with a manageable safety profile, offering a new targeted therapy option for patients with this aggressive blood cancer.

FDA Approves Novel Interchangeable Biosimilar for Pertuzumab in HER2+ Breast Cancer

The FDA has approved pertuzumab-dpzb (Poherdy) as the first interchangeable biosimilar to pertuzumab (Perjeta) for HER2-positive breast cancer. This designation means the biosimilar can be substituted for the reference product without a prescribing clinician’s consultation, depending on state pharmacy laws, significantly increasing patient accessibility and potentially lowering costs.

Pertuzumab-dpzb is approved for both metastatic and early-stage HER2-positive breast cancer, used in combination with trastuzumab (Herceptin) and chemotherapy. It demonstrated no clinically meaningful differences from the reference product in safety, purity, or potency, maintaining the same dosing regimen and critical safety warnings, including cardiac risks.

Five-Year CAR T Data Reflect Long-Term PFS in Multiple Myeloma

Five-year follow-up data from the CARTITUDE-1 trial of ciltacabtageneautoleucel (cilta-cel; Carvykti) demonstrates sustained, long-term progression-free survival in patients with relapsed/refractory multiple myeloma.

The trial, involving patients with a median of 6 prior lines of therapy, initially saw a 98% response rate. After 5 years, approximately 1/3 of the patients remain in remission, with minimal relapses after 36 months. Researchers noted that the majority of these long-term responders are minimal residual disease-negative, supporting the potential for B-cell maturation antigen-targeted chimeric antigen receptor (CAR) T-cell therapy to be considered a potentially curative treatment for multiple myeloma.

Behind the FDA’s Elimination of REMS Program for CAR T-Cell Therapies

Frederick Locke, MD, discusses the removal of the Risk Evaluation and Mitigation Strategy (REMS) program previously required for all commercially available CAR T-cell therapies. He notes how this decision follows years of real-world clinical experience and data showing that the initial risks, primarily neurotoxicity and cytokine release syndrome, are now well-understood and effectively managed by health care providers.

The REMS program, which necessitated specialized certification for facilities, will be replaced by standard clinical practice guidelines. Locke discusses how this change streamlines access to these life-saving treatments, easing the administrative burden on hospitals while maintaining patient safety, as clinicians have sufficient expertise for monitoring and managing these known adverse events.

A 25-Year Snapshot of Survival With Metastatic Breast Cancer and Brain Metastases

A 25-year retrospective study of patients with metastatic breast cancer (MBC) and brain metastases highlighted significant survival differences based on disease subtype and time of diagnosis.

Patients with HER2-positive MBC showed the longest median OS (31 months) and notable survival improvements in those diagnosed after 2014. Patients with triple-negative breast cancer had the shortest survival (12.8 months), though their outcomes also recently improved. Importantly, HER2-positive/HER2-negative patients showed no meaningful survival improvement over the period, underscoring an unmet clinical need for new systemic treatments for this subtype.