Sacituzumab tirumotecan (sac-TMT), an antibody-drug conjugate (ADC) targeting TROP2, has demonstrated promising antitumor activity in patients with pretreated advanced endometrial and ovarian cancers. Preliminary results from the phase 2 KL264-01 trial, presented at the 2024 ESMO Congress, reveal encouraging objective response rates and manageable safety profiles in these difficult-to-treat populations. These findings suggest that sac-TMT could offer a valuable new treatment option for patients who have progressed on prior lines of therapy.
The study's lead author, Dr. Danbo Wang, a professor in the Gynecology Department at Liaoning Cancer Hospital, China Medical University, highlighted the clinical significance of the results, stating, "Our study showed that sac-TMT monotherapy demonstrated promising antitumor activity in these previously treated patient populations with a manageable safety profile."
KL264-01 Trial Design and Key Findings
The KL264-01 trial enrolled patients with endometrial and ovarian cancers who had received at least one prior line of platinum-based chemotherapy and had an ECOG performance status of 0 or 1. Patients with MSI-H/dMMR endometrial cancer were required to have prior anti-PD-(L)1 therapy. Sac-TMT was administered at 5 mg/kg once every two weeks until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed ORR per RECIST 1.1 criteria.
In the endometrial cancer cohort (n = 44), the ORR was 34.1% (confirmed ORR 27.3%) with a disease control rate (DCR) of 75.0% at a median follow-up of 7.2 months. The median progression-free survival (PFS) was 5.7 months (95% CI, 3.7-9.4), and the median duration of response (DOR) was 5.7 months (range, 3.8 to 7.4+).
The ovarian cancer cohort (n = 40) showed an ORR of 40.0% (confirmed ORR 35.0%) and a DCR of 75.0% at a median follow-up of 28.2 months. The median PFS was 6.0 months (95% CI, 3.9-7.3), and the median DOR was 5.3 months (range, 2.1 to 24.4+).
Safety and Tolerability
Treatment-related adverse events (TRAEs) were observed in all patients across both cohorts. Grade 3 or higher TRAEs occurred in 72.7% of endometrial cancer patients and 67.5% of ovarian cancer patients. Common all-grade TRAEs included anemia (88.6% and 85.0%, respectively), decreased white blood cell count (81.8% and 60.0%), and decreased neutrophil count (65.9% and 57.5%). Serious TRAEs led to discontinuation of sac-TMT in 2.3% of endometrial cancer patients and 12.5% of ovarian cancer patients. No TRAEs led to death, and there were no reports of drug-related interstitial lung disease or pneumonitis.
Ongoing Research and Future Directions
Sac-TMT is currently being evaluated in the global phase 3 TroFuse-005 trial (NCT06132958), comparing it to physician's choice of chemotherapy in patients with advanced endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy. This trial aims to further establish the efficacy and safety of sac-TMT in this setting.
Kelun-Biotech has licensed the exclusive rights to MSD (Merck & Co., Inc) to develop, use, manufacture, and commercialize sac-TMT in all territories outside of Greater China. Sac-TMT has already been approved in China for 2L+ advanced triple-negative breast cancer (TNBC), and supplemental new drug applications (sNDA) are under review for 2L/3L EGFR-mutant non-small cell lung cancer (NSCLC).
