Sacituzumab Tirumotecan Shows Antitumor Activity in Previously Treated Endometrial, Ovarian Cancers

Sacituzumab tirumotecan (sac-TMT; formerly SKB264/MK-2870) monotherapy generated clinical activity in patients with previously treated advanced endometrial and ovarian cancers, according to findings from the phase 2 KL264-01 trial (NCT04152499).

Preliminary results presented at the 2024 ESMO Congress demonstrated that at a median follow-up of 7.2 months, patients in the endometrial cancer cohort (n = 44) experienced an objective response rate (ORR) of 34.1% per RECIST 1.1 criteria as assessed by investigators; the confirmed ORR was 27.3%. Patients in this cohort had a disease control rate (DCR) of 75.0%, a partial response (PR) rate of 34.1%, and a stable disease (SD) rate of 40.9%.

Preliminary data from the cohort of patients with ovarian cancer (n = 40) demonstrated that at a median follow-up of 28.2 months, the ORR was 40.0%, and the confirmed ORR was 35.0% Patients in this cohort had a DCR of 75.0%, a PR rate of 40.0%, and a SD rate of 35.0% (n = 14).

“Our study showed that sac-TMT monotherapy demonstrated promising antitumor activity in [these] previously treated [patient] populations with a manageable safety profile,” lead study author Danbo Wang, MD, PhD, a professor in the Gynecology Department at Liaoning Cancer Hospital, China Medical University, said in a presentation of the data.

KL264-01 Trial Design and Baseline Patient Characteristics

The study included patients with endometrial and ovarian cancers who received at least 1 prior line of platinum-based chemotherapy and had an ECOG performance status of 0 or 1. In the endometrial cancer cohort, patients with microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) disease were required to have prior treatment with anti–PD-(L)1 therapy. In the ovarian cancer cohort, at least 2 prior lines of platinum-based chemotherapy were necessary for patients with platinum-sensitive disease.

Sac-TMT was administered at 5 mg/kg once every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Tumors were assessed once every 8 weeks for the first 12 months and once every 12 weeks thereafter.

The trial’s primary end point was investigator-assessed ORR per RECIST 1.1 criteria; secondary end points included progression-free survival (PFS), duration of response (DOR), overall survival, and safety.

In the endometrial cancer cohort, the median age was 58 years (range, 40-73), and patients had an ECOG performance status of 0 (31.8%) or 1 (68.2%). The median age in the ovarian cancer cohort was 57.5 years (range, 29-74), and patients had an ECOG performance status of 0 (25.0%) or 1 (75.0%). A TROP2 immunohistochemistry (IHC) H-score of more than 200 was shown in 27.3% and 32.5% of patients from the endometrial and ovarian cancer cohorts, respectively. TROP2 IHC H-score of 200 or less was seen in 63.6% and 55.0% of patients, respectively.

In the endometrial cancer cohort, tumor histology included endometroid (54.5%), non-endometroid (31.8%), carcinosarcoma (6.8%), and unknown (6.8%). Only 1 patient (2.3%) had MSI-H/dMMR disease; however, this status was unknown or not tested in 27.3% of patients. Patients received either 1 prior line of systemic therapy (47.7%) or 2 or more prior lines of therapy (52.3%). Prior immunotherapy was given to 36.4% of patients with endometrial cancer.

In the ovarian cancer cohort, tumor histology included high-grade serous (62.5%), non–high-grade serous (20.0%), and other (17.5%). Twenty percent of patients previously received 2 lines of treatment, and 80.0% previously received 3 or more lines of systemic therapy. At study entry, 12.5% of patients had platinum-sensitive disease, and 87.5% had platinum-resistant disease.

At the data cutoff of March 5, 2024, 50.0% and 10.0% of patients from the endometrial and ovarian cancer cohorts, respectively, remained on sac-TMT monotherapy.

Additional Efficacy and Safety Data, Plus Next Steps

The median PFS among patients from the endometrial and ovarian cancer cohorts was 5.7 months (95% CI, 3.7-9.4) and 6.0 months (95% CI, 3.9-7.3), respectively. 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 effects (TRAEs) occurred in 100% of patients in both cohorts. Grade 3 or higher TRAEs occurred 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 patients with endometrial cancer and 12.5% of patients with ovarian cancer.

“We found [similarities in the] safety profile in these two cohorts. The most common [hematologic] TRAEs were anemia, [decreased] white blood cell [count], and [decreased] neutrophil count,” Wang explained.

Specifically, common all-grade TRAEs included anemia in (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%).

Of note, no TRAEs led to death, and there were no reports of drug-related interstitial lung disease or pneumonitis.

Sac-TMT monotherapy is being further evaluated vs 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).

Reference

Wang D, Wang K, An R, et al. Safety and efficacy of sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC) from a phase II study. Ann Oncol. 2024;35(suppl 2):S548. doi:10.1016/j.annonc.2024.08.777