715MO - 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

Background

Trophoblast cell surface antigen 2 (TROP2) is highly expressed in EC and OC. Sac-TMT (also known as MK-2870/SKB264) is a TROP2 ADC developed with a hydrolytically cleavable linker to conjugate a belotecan-derivative topoisomerase I inhibitor. Here, we report the preliminary results from a Phase 2 study in pts with advanced EC and OC (KL264-01, NCT04152499).

Methods

Advanced EC and OC pts who have been previously treated with platinum-based chemo were given sac-TMT at 5 mg/kg Q2W until disease progression, unacceptable toxicity or withdrawal of consent. Tumor assessment was performed every 8 weeks per RECIST v1.1 by investigator. The TROP2 expression was scored using the semi-quantitative H-score method, and cut-off point was set to 200.

Results

As of March 5, 2024, 44 EC pts were enrolled and median follow-up time was 7.2 mo. 52.3% of pts had received ≥ 2 prior lines of therapy. The ORR was 34.1% (15/44, 12 confirmed) and DCR was 75%. Median PFS was 5.7 mo (95% CI: 3.7, 9.4) with 6-mo PFS rate of 47.5%. In the pts with TROP2 IHC H-score > 200 (n=12) or H-score ≤ 200 (n=28), the ORR was 41.7% (5/12, 3 confirmed) and 35.7% (10/28, 9 confirmed) respectively. 40 OC pts were enrolled and median follow-up time was 28.2 mo. All pts had received ≥ 2 prior lines of therapy (80% of pts ≥ 3 prior lines). 87.5% of pts were platinum-resistant. The ORR was 40% (16/40, 14 confirmed) and DCR was 75%. mPFS was 6.0 mo (95% CI: 3.9, 7.3); mOS was 16.5 mo (95% CI: 10.7, NE). In the pts with TROP2 IHC H-score > 200 (n=13) or H-score ≤ 200 (n=22), the ORR was 61.5% (8/13, 7 confirmed) and 27.3% (6/22, 6 confirmed) respectively. In the pts with platinum-resistant (n=35), mPFS was 6.0 mo (95% CI: 5.3, 7.3) and mOS was 16.1 mo (95% CI: 10.5, NE). Safety of the EC and OC pts is presented in the table. Table: 715MO

Safety summary

Conclusions

Sac-TMT monotherapy has shown promising anti-tumor activity with a manageable safety profile in pts with heavily pre-treated advanced EC and OC.

Clinical trial identification

NCT04152499; first posted on November 5, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, China.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

B. Akala, E. Chartash: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc., Rahway, NJ, USA. Y. Li, X. Li, X. Jin, J. Ge: Financial Interests, Personal, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.