The Targeted Pulse: Tune-In to Discover The Most Recent FDA Approvals and Investigators’ Captivating Findings in Glioblastoma and Brain Mets Therapy

Zenocutuzumab Gains Gold With FDA Approval in NSCLC and Pancreatic Cancer

Zenocutuzumab (formerly MCLA-128) has received FDA approval for the treatment of patients with neuregulin 1 fusion (NRG1+) non–small cell lung cancer (NSCLC) and NRG1+ pancreatic ductal adenocarcinoma (PDAC). This approval is based on data from the open-label, multicenter, dose-escalation phase 1/2 eNRGy trial (NCT0291294). In the trial, investigators established a recommended dose of 750 mg administered every 2 weeks for patients with either NSCLC or PDAC.

“Zenocutuzumab is highly effective in pretreated NRG1 fusion-positive pancreatic cancer, with rapid and durable responses. There is activity across multiple NRG1 fusion-positive cancer types and an extremely well-tolerated safety profile,” said Alison M. Schram, MD, lead study author and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, during a presentation of the data.

Sacituzumab Tirumotecan Advances in EGFR+ NSCLC With Breakthrough Status

Sacituzumab tirumotecan (SKB264/MK-2870) has received breakthrough therapy designation from the FDA. The designation applies to patients with advanced or metastatic nonsquamous EGFR mutated NSCLC that has progressed after receiving a tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Data from a phase 2 expansion cohort are the basis for this decision. Sacituzumab govitecan, a TROP2-targeted antibody-drug conjugate (ADC), is also undergoing evaluation in combination with pembrolizumab (Keytruda) for NSCLC in 3 other trials: NCT06170788, NCT06422143, and NCT06312137.

“This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous NSCLC. We believe ADCs are an important modality in the treatment of cancer and are rapidly advancing the clinical development of sacituzumab tirumotecan, with the goal of meaningfully improving upon current standards of care in certain cancers.” said Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, in a press release.

Durvalumab Finishes The Race With FDA Approval in Small Cell Lung Cancer

Durvalumab (Imfinzi) has gained FDA approval for patients with limited-stage small cell lung cancer (SCLC) who have not progressed after treatment with platinum-based concurrent chemoradiotherapy. This approval is supported by data from the phase 3 ADRIATIC study (NCT03703297). In the trial, durvalumab was compared with placebo and demonstrated improved overall survival, with no new safety signals.

“I think this establishes a new standard of care for the treatment of limited-SCLC. That is, chemotherapy and radiation should continue to be the core treatment of those patients. But after that is completed and patients are safe, and there are no other issues, they should go on to receive up to 2 years of durvalumab given monthly because of these benefits that have been seen in this study,” said David Spigel, MD, told Targeted Oncology^TM in an interview.

Spigel is chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, and primary investigator of the trial.

Sonodynamic Therapy Doubles OS and Triples PFS in Recurrent Glioblastoma

Treatment with sonodynamic therapy (SDT)more than doubled median OS and tripled progression-free survival (PFS) in patients with recurrent or refractory high-grade gliomas when compared with historical outcomes. These data come from afirst-in-human, phase 1/2 clinical trial (NCT05362409), presented at the 2024 Society of Neuro-Oncology (SNO) Annual Meeting.

“In addition to the strong safety data and early indications of efficacy, Alpheus' non-invasive SDT therapy stands out for its ease of use - a significant improvement over the uncomfortable and often toxic treatments currently available for this rapidly fatal condition,” stated Michael Schulder, MD, Director of the Brain Tumor Center at Northwell Health, and one of the trial's primary investigators, during the SNO presentation. “We look forward to expanding the ability for patients to receive this promising therapy.”

Systemic Therapy Selection Plays Pivotal Role in Brain Metastases

Choosing the right systemic therapy is crucial for improving outcomes in patients with brain metastases, according to new research from Rupesh Kotecha, MD, at the Miami Cancer Institute. In an interview with Targeted Oncology^TM, Kotecha discussed the complexity of systemic therapy decisions and their impact on overall patient outcomes. He also highlighted future steps to better understand the relationship between these factors, noting that these data will become increasingly important as patients transition to receiving systemic therapy alone.

“We found that the systemic therapy choice had a specific correlation with intracranial PFS. For instance, patients treated with chemotherapy alone, chemotherapy plus immunotherapy, or chemotherapy with targeted therapies showed distinct differences in intracranial PFS,” Kotecha said in the interview.

Kotecha is chief of radiosurgery and director of central nervous system metastasis with Baptist Health Miami Cancer Institute.

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