386P - Exploratory analysis of patients with or without prior PD-(L)1 inhibitors in phase III OptiTROP-Breast01 study of sacituzumab tirumotecan (sac-TMT) versus chemotherapy for previously treated advanced triple-negative breast cancer (TNBC)

Background

Sac-TMT (also known as SKB264/MK-2870) is a TROP2 ADC developed with a hydrolytically cleavable linker to conjugate the payload T030, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio of 7.4. The pivotal phase III OptiTROP-Breast01 study (NCT05347134), presented at the 2024 ASCO meeting, demonstrated improved survival outcomes with sac-TMT over chemotherapy in patients with pretreated advanced TNBC. This exploratory analysis from OptiTROP-Breast01 study evaluates the impact of prior PD-(L)1 inhibitors on clinical outcomes.

Methods

Patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, with at least one given in the metastatic setting, were randomized to receive either sac-TMT or treatment of physician’s choice (TPC: eribulin, capecitabine, gemcitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR).

Results

As of Nov 30, 2023, prior PD-(L)1 inhibitors were received in 24.6% (32/130) of patients treated with sac-TMT and 27.1% (36/133) treated with TPC. Clinical benefit was observed with sac-TMT versus TPC in this subgroup. The median PFS by BICR was 5.6 versus 2.7 months (HR 0.31; 95% CI 0.17-0.54), and objective response rate (ORR) by BICR was 56.3% versus 5.6%. For those patients who didn’t receive prior PD-(L)1 inhibitors, efficacy outcomes were similarly improved with sac-TMT versus TPC. The median PFS was 7.2 versus 2.3 months (HR 0.34; 95% CI 0.23-0.48), and ORR was 41.8% versus 14.4%. Safety data in the sac-TMT arm were similar between patients with or without prior PD-(L)1 inhibitors.

Conclusions

This exploratory analysis suggests that treatment with sac-TMT results in better outcomes than TPC for previously treated locally recurrent or metastatic TNBC patients regardless of prior PD-(L)1 therapy, supporting sac-TMT as an effective treatment option in this population.

Clinical trial identification

NCT05347134; first posted on April 26, 2022.

Editorial acknowledgement

Legal entity responsible for the study

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

Funding

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

Disclosure

X. Jin; Y. Diao; G. Liu; 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.