ASCO24: Merck’s TROP2 ADC Reduces TNBC Progression, Death Risk by 69%

Merck & Co.'s sacituzumab tirumotecan, a TROP2-targeting antibody-drug conjugate (ADC), has shown promising results in reducing the risk of disease progression or death in patients with advanced triple-negative breast cancer (TNBC). This breakthrough was highlighted in the Phase III OptiTROP-Breast01 trial, whose findings were released in advance of the American Society of Clinical Oncology (ASCO) annual meeting.

Sacituzumab tirumotecan, also known by its identifiers MK-2870 or SKB264, was acquired by Merck from Kelun-Biotech in 2022. Since then, Merck has been advancing the drug through various clinical stages, including pivotal trials for non-small-cell lung cancer and early-stage combination trials with Keytruda (pembrolizumab), Merck's anti-PD1 therapy.

The OptiTROP-Breast01 trial, conducted in China, involved 263 patients with locally recurrent or metastatic TNBC who had undergone at least two previous treatments, including one for the metastatic setting. These patients were divided into two groups: one receiving sacituzumab tirumotecan and the other receiving the physician's choice of chemotherapy. The primary objective of the study was to assess progression-free survival (PFS), which was confirmed at an interim analysis in August of the previous year, paving the way for a marketing application in China.

The detailed results, now available ahead of the ASCO meeting, indicate that sacituzumab tirumotecan significantly outperformed chemotherapy. Patients treated with sacituzumab tirumotecan had a median PFS of 5.7 months compared to just 2.3 months for those on chemotherapy. Additionally, the six-month PFS rates were 43.4% for sacituzumab tirumotecan and 11.1% for chemotherapy. Notably, in patients with higher TROP2 expression, sacituzumab tirumotecan achieved a median PFS of 5.8 months, versus 1.9 months with chemotherapy, resulting in a hazard ratio (HR) of 0.28.

Moreover, the trial's initial overall survival (OS) analysis, with a data cut-off in November of the previous year, indicated a statistically significant OS benefit for sacituzumab tirumotecan. With a median follow-up of 10.4 months, the HR for OS favored sacituzumab tirumotecan at 0.53. While the median OS had not been reached for the sacituzumab tirumotecan group, it was noted to be 9.4 months for those receiving chemotherapy. The objective response rates were also notably higher in the sacituzumab tirumotecan group at 43.8%, compared to 12.8% for chemotherapy.

Safety analysis revealed that the most common Grade 3 or higher treatment-related adverse events for sacituzumab tirumotecan included decreases in neutrophil counts (32.3% vs. 47% in chemotherapy), white blood cell counts (25.4% vs. 36.4%), and anemia (27.7% vs. 6.1%).

The findings from this trial highlight sacituzumab tirumotecan's potential to significantly improve outcomes for patients with advanced TNBC, marking a major step forward in cancer treatment. However, competition in the TROP2 ADC space is intensifying. Gilead Sciences' Trodelvy (sacituzumab govitecan) already has FDA approval for similar indications, including TNBC and urothelial cancer. AstraZeneca and Daiichi Sankyo are also developing their TROP2-directed ADC, datopotamab deruxtecan, which is currently under review for non-small-cell lung and breast cancers in Europe and the U.S.

These developments underscore the dynamic nature of cancer treatment research, particularly in the TROP2-targeting ADC domain, which continues to evolve with new therapies and clinical advancements.