Sacituzumab tirumotecan (sac-TMT), formerly known as SKB264/MK-2870, has demonstrated clinical activity in patients with previously treated advanced endometrial and ovarian cancers. These findings come from the phase 2 KL264-01 trial (NCT04152499), with preliminary results presented at the 2024 ESMO Congress.
Efficacy in Endometrial Cancer
The endometrial cancer cohort (n = 44) showed an objective response rate (ORR) of 34.1% per RECIST 1.1 criteria, as assessed by investigators, with a confirmed ORR of 27.3%. The disease control rate (DCR) was 75.0%, with a partial response (PR) rate of 34.1% and a stable disease (SD) rate of 40.9%. At a median follow-up of 7.2 months, these results indicate a clinically meaningful response in a heavily pretreated population.
Efficacy in Ovarian Cancer
Preliminary data from the ovarian cancer cohort (n = 40) revealed an ORR of 40.0%, with a confirmed ORR of 35.0%. The DCR was also 75.0%, comprising a PR rate of 40.0% and an SD rate of 35.0% (n = 14). The median follow-up for this cohort was 28.2 months, suggesting durable responses in some patients.
Investigator Comments
"Our study showed that sac-TMT monotherapy demonstrated promising antitumor activity in these previously treated patient populations with a manageable safety profile," said lead study author Danbo Wang, MD, PhD, a professor in the Gynecology Department at Liaoning Cancer Hospital, China Medical University.
Trial Design and Patient Characteristics
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 microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) endometrial cancer were required to have prior treatment with anti–PD-(L)1 therapy. For the ovarian cancer cohort, patients with platinum-sensitive disease needed at least two prior lines of platinum-based chemotherapy.
Sac-TMT was administered at 5 mg/kg once every two weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Tumors were assessed every eight weeks for the first 12 months and every 12 weeks thereafter. The primary endpoint was investigator-assessed ORR per RECIST 1.1 criteria, with secondary endpoints including progression-free survival (PFS), duration of response (DOR), overall survival, and safety.
Additional Efficacy and Safety Data
The median PFS was 5.7 months (95% CI, 3.7-9.4) in the endometrial cancer cohort and 6.0 months (95% CI, 3.9-7.3) in the ovarian cancer cohort. The median DOR was 5.7 months (range, 3.8 to 7.4+) and 5.3 months (range, 2.1 to 24.4+) in the respective cohorts.
Treatment-related adverse events (TRAEs) occurred in 100% of patients in both cohorts. Grade 3 or higher TRAEs were observed in 72.7% and 67.5% of patients from the endometrial and ovarian cancer cohorts, respectively. Serious TRAEs occurred in 20.5% and 37.5% of patients, respectively, with TRAEs leading to discontinuation of sac-TMT in 2.3% of endometrial cancer patients and 12.5% of ovarian cancer patients.
Common all-grade TRAEs included anemia (endometrial cohort, 88.6%; ovarian cohort, 85.0%), decreased white blood cell count (81.8%; 60.0%), decreased neutrophil count (65.9%; 57.5%), stomatitis (38.6%; 57.5%), vomiting (36.4%; 40.0%), nausea (27.3%; 42.5%), decreased platelet count (25.0%; 42.5%), and rash (15.9%; 32.5%). Notably, no TRAEs led to death, and there were no reports of drug-related interstitial lung disease or pneumonitis.
Ongoing Phase 3 Trial
Sac-TMT monotherapy is being further evaluated versus physician’s choice of chemotherapy in patients with advanced endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy in the ongoing, global phase 3 TroFuse-005 trial (NCT06132958).
