Lung Cancer Breakthroughs: Key Advancements and FDA Decisions This Week

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw advancements in lung cancer and FDA decisions. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week. Addition of Lurbinectedin Improves Duration of Maintenance in ES-SCLC The phase 3 IMforte trial demonstrated that adding lurbinectedin (Zepzelca) to atezolizumab maintenance significantly improves outcomes in extensive-stage small cell lung cancer (ES-SCLC). Among 483 patients who did not progress after platinum-etoposide-atezolizumab induction, the doublet reduced the risk of disease progression by 46% (HR, 0.54). Median progression-free survival (PFS) reached 5.4 vs 2.1 months with atezolizumab alone. Overall survival also improved (13.2 vs 10.6 months; HR, 0.73). While grade 3/4 treatment-related adverse events were higher in the combination arm (25.6% vs 5.8%), primarily due to manageable cytopenias, discontinuation rates remained low (6.2%). This regimen establishes a new first-line maintenance standard for ES-SCLC. For a Second Time, FDA Denies Approval of Tab-Cel in EBV+ PTLD The FDA has issued a second complete response letter (CRL) for tabelecleucel (tab-cel; Ebvallo), an allogeneic T-cell immunotherapy for Epstein-Barr virus–positive posttransplant lymphoproliferative disease (EBV+ PTLD). While previous manufacturing concerns were resolved, the FDA now deems the single-arm phase 3 ALLELE trial insufficient for accelerated approval, citing concerns regarding study design and potential confounding. Despite a significant 48.8% objective response rate and breakthrough therapy status, this regulatory shift reverses years of prior alignment. Currently approved in Europe, tab-cel remains an investigational agent in the US, leaving a critical unmet need for relapsed/refractory EBV+ PTLD patients. Patient Case #2: Newly Diagnosed Stage 3B NSCLC Optimal management of early-stage non-small cell lung cancer (NSCLC) necessitates the synthesis of diagnostic imaging, laboratory data, and comprehensive molecular profiling. While staging and surgical respectability remain primary considerations, reflex next-generation sequencing is essential to identify actionable drivers that dictate neoadjuvant or adjuvant strategies. Furthermore, PD-L1 expression levels guide the integration of immunotherapy, which may still offer clinical benefit in PD-L1-negative tumors when paired with platinum-based chemotherapy. By leveraging molecular data and clinical risk factors, clinicians can refine the sequencing of multimodal interventions—surgery, systemic therapy, and surveillance—to enhance pathologic response and long-term survival. FDA Receives BLA for Ivonescimab in EGFR+ NSCLC A biologics license application has been submitted to the FDA for ivonescimab (AK112) in combination with chemotherapy for patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC following progression on a third-generation tyrosine kinase inhibitor. Ivonescimab is a first-in-class bispecific antibody designed to simultaneously inhibit PD-1 and VEGF. The application is supported by the phase 3 HARMONi trial, which demonstrated a statistically significant improvement in PFS. Median PFS was 6.8 months with ivonescimab-chemotherapy vs 4.4 months with chemotherapy alone (HR, 0.52). Benefit was consistent across subgroups, including those with brain metastases (HR, 0.40). If approved, ivonescimab would establish a novel second-line standard of care. Remaining Unmet Needs in Biomarker Testing in Early-stage NSCLC In early-stage NSCLC, biomarker testing is increasingly vital for guiding neoadjuvant and adjuvant strategies, yet significant unmet needs persist. Clinical data indicate that testing rates in early-stage disease lag behind metastatic settings, with less than 40% of stage I–III patients receiving comprehensive next-generation sequencing. Key barriers include limited tissue availability from small biopsies, prolonged turnaround times that delay definitive surgery or systemic therapy, and a lack of standardized "reflex" testing protocols. Furthermore, socioeconomic disparities and geographic variations in access to high-sensitivity assays—such as liquid biopsy for minimal residual disease monitoring—hinder the shift toward truly personalized, precision-based curative intent care.