OptiTROP-Breast05: Sacituzumab Tirumotecan Shows 71% ORR in Advanced TNBC

Sacituzumab tirumotecan (sac-TMT) shows promising anti-tumor activity and a manageable safety profile as a first-line treatment for patients with unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC), according to results of the phase II OptiTROP-Breast05 study presented as an abstract at the 2025 American Society of Clinical Oncology Annual Meeting.

“TROP2 (trophoblast cell surface antigen 2) is highly expressed in TNBC and associated with poor survival,” explained the investigators. “Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. It is approved in China for pts with a/mTNBC who have received at least two prior chemotherapies, including one for metastatic disease.”

The Phase II OptiTROP-Breast05 study (ClinicalTrials.gov ID: NCT05445908) is evaluating the safety and tolerability, as well as the preliminary antitumor activity, of sac-TMT as a first-line treatment for patients with a/mTNBC. The investigators also evaluated the impact of PD-L1 combined positive score (CPS) status.

The study enrolled patients with a/mTNBC and no prior treatment for advanced disease, regardless of PD-L1 or TROP2 status, to receive sac-TMT (5 mg/kg, every 2 weeks) until disease progression or unacceptable toxicity. Patients with recurrent TNBC were required to have a disease-free interval of at least 6 months. The investigators performed tumor assessment every 6 weeks (per RECIST v1.1).

As of November 18, 2024, the study enrolled 41 patients (median age, 55 years; ECOG PS 1, 43.9%; PD-L1 CPS <10, 78.0%). At baseline, 61.0% of patients had visceral metastases, and 29.3% of patients had de novo metastasis. For recurrent TNBC, 19.5% of patients had a disease-free interval of 6-12 months, and 51.2% of patients had a disease-free interval of more than 12 months. The median follow-up duration was 18.6 months.

For the overall cohort, the investigators reported an objective response rate (ORR) of 70.7%, disease control rate (DCR) of 92.7%, median duration of response of 12.2 months, median progression-free survival (mPFS) of 13.4 months, and 12-month PFS rate of 64.6% (95% confidence interval [CI], 45.0-78.7%).

Among patients with PD-L1 CPS less than 10, the study team observed an ORR of 71.9%, DCR of 93.8%, mPFS of 13.1 months, and 12-month PFS rate of 59.1% (95% CI, 37.1-75.7%).

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 63.4% of patients. The most common (occurring in ≥5% of patients) were decreased neutrophil count (46.3%), decreased white blood cell count (34.1%), anemia (12.2%), stomatitis (9.8%), decreased lymphocyte count (7.3%), and fatigue (7.3%). The investigator reported no treatment-related deaths and no neuropathy or interstitial lung disease/pneumonitis.

“Sac-TMT demonstrated promising anti-tumor activity with a manageable safety profile as a first-line treatment for [patients] with a/mTNBC, independent of the PD-L1 status,” concluded the investigators. “A Phase 3 study comparing sac-TMT vs investigator’s choice of chemotherapy in first-line PD-L1-negative (CPS < 10) a/mTNBC is currently underway (NCT06279364).”

Disclosure: This research was supported by Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Please see the original reference for a full list of disclosures.