The Targeted Pulse: the Latest Oncology Advances

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 and FDA decisions, bringing renewed hope to patients and clinicians alike. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

Trastuzumab Pamirtecan Shows Efficacy in Phase 3 for HER2-Positive Breast Cancer

The phase 3 DYNASTY-Breast01 study has met its primary end point, showing that the novel antibody-drug conjugate (ADC) trastuzumab pamirtecan (BNT323/DB-1303) is effective in treating HER2-positive unresectable or metastatic breast cancer. The study, conducted in China, compared trastuzumab pamirtecan to trastuzumab emtansine (T-DM1) in patients previously treated with trastuzumab and a taxane. The new drug, a third-generation topoisomerase-1 inhibitor-based ADC, selectively targets cancer cells and is also being investigated in a separate global trial for HER2-low metastatic breast cancer, suggesting its potential for broader use.

Lurbinectedin Maintenance Yields Improved Survival in ES-SCLC

During a live event, Tejas Patil, MD, discussed how research is focused on improving long-term survival for patients with extensive-stage small cell lung cancer (ES-SCLC). While immunotherapy with agents like atezolizumab and durvalumab has shown durable responses in a small percentage of patients, new strategies are being explored. A key advancement is the IMforte trial, which investigated adding lurbinectedin as a maintenance therapy after initial chemotherapy with atezolizumab. The study met its primary endpoints, demonstrating a significant improvement in both progression-free and overall survival for patients receiving the lurbinectedin-immunotherapy combination, representing a new and promising approach to managing ES-SCLC.

FDA Approves Intravesical Gemcitabine Delivery for Bladder Cancer

The FDA has approved Inlexzo (formerly TAR-200), a gemcitabine intravesical delivery system, a novel bladder-sparing therapy for adults with certain types of BCG-unresponsive non–muscle-invasive bladder cancer. Inlexzo is an intravesical drug-releasing system that provides extended, local delivery of gemcitabine directly into the bladder. The approval is based on data from the phase 2b SunRISe-1 study, which demonstrated that 82% of patients achieved a complete response. Significantly, 51% of these patients maintained their response for at least 1 year. The treatment offers an important alternative to radical cystectomy for eligible patients, with a manageable safety profile.

The BOT/BAL Breakthrough: A New Era for Colorectal Cancer Treatment

A clinical trial for the immunotherapy combination of botensilimab and balstilimab (BOT/BAL) shows promise for treating advanced colorectal cancer, a disease with a significant unmet need for effective immunotherapy. Benjamin Schlechter, MD, explains that while chemotherapy is the current standard, BOT/BAL works by activating and sustaining the body’s immune response against cancer. The phase 1 trial demonstrated unexpected efficacy in patients with advanced colorectal cancer without liver metastases, even in those who had undergone extensive prior treatments. These findings are particularly significant as they represent a new class of drugs for a patient population that has long lacked viable immunotherapy options. The next step is a planned phase 3 trial to pursue regulatory approval.

Taletrectinib's Sustained Efficacy in Advanced ROS1-Positive NSCLC

Updated results from the phase 2 TRUST-II study of taletrectinib (Ibrtrozi) for advanced ROS1-positive non–small cell lung cancer (NSCLC) show impressive and durable responses. The study, which includes treatment-naive and pretreated patients, demonstrated an 85% objective response rate in the former and a 61.7% rate in the latter. Progression-free survival medians were not yet reached in treatment-naïve patients. The drug has a favorable safety profile with transient gastrointestinal side effects and a significantly lower incidence of neurological side effects compared to other approved drugs. This data, presented at the WCLC, supports taletrectinib as a dominant new option for ROS1-positive NSCLC.