The Targeted Pulse: ESMO Highlights and FDA Actions

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw several breakthroughs in targeted therapies, FDA decisions, and live updates from the 2025 European Society for Medical Oncologists (ESMO) Congress. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

After Setbacks, FDA Approves BelantamabMafodotin Combo in Myeloma

The FDA has approved belantamabmafodotin (Blenrep) in combination with bortezomib and dexamethasone (BVd) for adult patients with relapsed or refractory multiple myeloma who have received at least 2 prior lines of therapy. This approval follows a previous withdrawal of the drug's monotherapy approval.

The decision is based on data from the phase 3 DREAMM-7 trial, which demonstrated a statistically significant overall survival benefit and an improvement in progression-free survival (PFS) for the BVd regimen vs the standard-of-care daratumumab (Darzalex) combination. Despite a divided Oncologic Drugs Advisory Committee vote due to concerns over high rates of ocular toxicity and dosage uncertainty, the drug offers a much-needed, community-accessible BCMA-targeting option for patients.

Sustained Abemaciclib Benefit in High-Risk Breast Cancer: MonarchE Trial Update

The monarchE trial's primary overall survival (OS) analysis presented at ESMO 2025 confirms that 2 years of adjuvantabemaciclib(Verzenio) plus endocrine therapy (ET) provides a statistically significant and clinically meaningful OS benefit for patients with high-risk, HR-positive, HER2-negative, node-positive early breast cancer.

The combination therapy reduced the risk of death by 15.8% compared with ET alone, representing the first contemporary medicine to show an OS improvement in this setting in over 2 decades. The update, with a median follow-up of 6.3 years, also demonstrated sustained improvements in invasive disease-free survival and distant relapse-free survivalfor up to 7 years. Safety findings were consistent with previous analyses, validating abemaciclib plus ET as a standard-of-care.

Cancer Antigen mRNA-4359 Shows Increased Efficacy in Patients with Melanoma

Early phase 1/2 data for the investigational cancer antigen therapymRNA-4359 combined with pembrolizumab (Keytruda), shows promising efficacy in patients with advanced melanoma who were previously treated with checkpoint inhibitors.

The study reported a 24% overall objective response rate in the refractory patient population. Notably, the efficacy significantly increased to a 67% ORR in the subgroup of patients whose tumors were PD-L1–positive. mRNA-4359 is designed to encode antigens for PD-L1 and IDO1, aiming to generate a targeted T-cell response to counter tumor-induced immunosuppression. The combination was generally well-tolerated, supporting further investigation of this novel mRNA approach in hard-to-treat solid tumors.

Durvalumab Plus FLOT Improves OS in G/GEJ Adenocarcinoma

The phase 3 MATTERHORN trial demonstrated that adding the immunotherapy agent durvalumab to perioperative FLOT chemotherapy (5-FU, leucovorin, oxaliplatin, and docetaxel) significantly improved OS in patients with resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

The combination regimen showed a 22% reduction in the risk of death (HR, 0.78) compared with FLOT alone. This OS benefit was consistent across PD-L1 expression status. Earlier data also showed significant gains in event-free survival (EFS) and pathological complete response rates (pCR). These results strongly support the durvalumab-plus-FLOT regimen as a new global standard –ofcare for localized G/GEJ adenocarcinoma.

Sac-TMT Improves PFS in HR+/HER2– Metastatic Breast Cancer

The phase 3 OptiTROP-Breast02 trial demonstrated that the TROP2-targeted antibody-drug conjugate (ADC)sacituzumabtirumotecan (sac-TMT)provided a statistically significant and clinically meaningful benefit over standard chemotherapy in patients with previously treated HR-positive, HER2-negative metastatic breast cancer.

Sac-TMT achieved a median PFS of 8.3 months, approximately double the 4.1 months seen with chemotherapy, corresponding to a 65% reduction in the risk of disease progression or death. The efficacy was consistent across subgroups, including both HER2-low and HER2-zero disease. Sac-TMT exhibited a manageable safety profile, supporting its potential as a new therapeutic option for this patient population.