This week in oncology has been marked by significant progress across various cancer types, with new FDA approvals, guideline updates, and groundbreaking trial results offering new hope and treatment paradigms for clinicians and their patients. Here is a look at the top five developments shaping the field.
FDA Grants Accelerated Approval to Zongertinib in HER2+ NSCLC
The landscape for non-small cell lung cancer (NSCLC) patients with HER2 mutations is evolving with the accelerated FDA approval of zongertinib (Hernexeos). This targeted therapy is specifically indicated for patients with unresectable or metastatic nonsquamous NSCLC who have HER2 tyrosine kinase domain (TKD) activating mutations and have progressed after prior systemic therapy. Notably, this approval was accompanied by the clearance of the Oncomine Dx Target Test as a companion diagnostic, underscoring the importance of precise patient selection in the era of personalized medicine.
The approval is supported by compelling data from the phase 1 Beamion LUNG-1 study. In a cohort of patients who had undergone prior platinum-based chemotherapy, zongertinib demonstrated a remarkable overall response rate of 75%. Even more encouraging, 58% of these responders maintained a response duration of at least six months. Zongertinib’s unique mechanism of action as a highly selective HER2 TKI, without inhibiting EGFR, is designed to reduce the off-target toxicities often associated with older TKIs. While treatment-related adverse events were common, the proportion of grade 3 or higher events was manageable. This approval is a significant milestone, providing a new, targeted option for a patient population with a critical unmet need.
FDA Accepts NDA for Vepdegestrant in ER+, HER2- Metastatic Breast Cancer
In the metastatic breast cancer space, the FDA has accepted a new drug application (NDA) for vepdegestrant, a groundbreaking oral PROteolysis TArgeting Chimera (PROTAC) being developed by Arvinas and Pfizer. Vepdegestrant is being evaluated as a monotherapy for patients with ER+, HER2–, ESR1-mutated advanced or metastatic breast cancer who have already received prior endocrine-based therapy.
The submission is based on the impressive results of the phase 3 VERITAC-2 trial, which compared vepdegestrant to fulvestrant, the current standard of care. The data revealed a significant improvement in progression-free survival (PFS) in the ESR1-mutated subgroup, with a median PFS of 5.0 months for vepdegestrant vs just 2.1 months for fulvestrant. Vepdegestrant’s PROTAC mechanism, which induces the degradation of estrogen receptors, represents a novel approach to overcoming resistance to traditional endocrine therapies. If approved on its PDUFA date of June 5, 2026, vepdegestrant could emerge as a new “best-in-class” option for this patient population, offering a much-needed new therapeutic strategy.
Neoadjuvant Pembrolizumab and Enfortumab Vedotin Improve Outcomes in MIBC
A new analysis of the phase 3 KEYNOTE-905/EV-303 trial is poised to change the standard of care for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy. The study demonstrated that a combination of neoadjuvant pembrolizumab and enfortumab vedotin followed by radical cystectomy significantly improved event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rates.
The trial, which included 595 patients, compared the combination regimen to surgery alone. The positive outcomes suggest this therapeutic approach could become a new treatment paradigm, offering a highly effective option for a population with limited choices. While the safety profile was largely consistent with what has been observed for each drug individually, clinicians should be vigilant for specific adverse events such as skin reactions and pneumonitis/interstitial lung disease. This data is expected to be presented at an upcoming medical meeting, and regulatory submissions are planned, paving the way for this promising new regimen to reach patients.
NCCN Updates Small Cell Lung Cancer Guidelines with New LEMS Recommendations
The National Comprehensive Cancer Network (NCCN) has released an important update to its guidelines for small cell lung cancer (SCLC) to include new recommendations for managing Lambert-Eaton Myasthenic Syndrome (LEMS). This rare neuromuscular disorder, which often co-occurs with SCLC, can significantly impact patient quality of life. The updated guidelines now recommend neurological evaluation and testing for voltage-gated calcium channels (VGCCs) as part of the diagnostic process for SCLC patients.
Crucially, the guidelines also advise considering treatment with amifampridine (Firdapse), the only FDA-approved therapy for LEMS. A key phase 3 trial showed amifampridine improved muscle strength and a patient’s self-assessment of treatment efficacy compared to placebo. By integrating these recommendations, the NCCN aims to increase awareness and improve the diagnosis and management of this serious, and often overlooked, condition, ultimately enhancing the overall care for SCLC patients.
FDA Clears Novel Combination Trial for Recurrent Glioblastoma
There is renewed hope for patients with recurrent glioblastoma, a highly aggressive brain cancer, following the FDA’s clearance of a new phase 1b/2a clinical trial. This trial, sponsored by Starlight Therapeutics, will investigate the combination of the investigational drug STAR-001 with spironolactone. This innovative therapeutic strategy is based on the principle of synthetic lethality, where STAR-001 targets DNA damage repair deficiencies in cancer cells, while spironolactone enhances this effect by causing a deficiency in nucleotide excision repair.
The synergistic combination aims to make glioblastoma cells more vulnerable to the cytotoxic effects of STAR-001, providing a powerful one-two punch against this resilient cancer. This strategy was developed using Lantern Pharma’s AI platform, RADR®, which helped identify the optimal drug combination. The trial, expected to begin in late 2025 or early 2026, will enroll adults whose glioblastoma has recurred after initial therapy. This trial represents a significant step forward in leveraging artificial intelligence and novel therapeutic mechanisms to address one of oncology’s most persistent challenges.
