380MO - SKB264 (MK-2870) in previously treated hormone receptor-positive (HR+)/ HER2-negative metastatic breast cancer (mBC): Results from a phase I/II, single-arm, basket trial

Background

TROP2 is commonly overexpressed in HR+/HER2- mBC and associated with poor prognosis. SKB264 is a novel anti-TROP2 ADC developed using sulfonyl pyrimidine-CL2A-carbonate linker to conjugate its payload, a belotecan-derivative topoisomerase I inhibitor, to achieve an average Drug-to-antibody Ratio (DAR) of 7.4. This is the first report of results from a phase II cohort in patients (pts) with HR+/HER2- mBC.

Methods

Pts with HR+/HER2- (including HER2-low and HER2-zero) mBC received SKB264 at a dose of 5 mg/kg Q2W until progression or unacceptable toxicity. Eligibility included progression on endocrine-based therapy and at least one prior chemotherapy for mBC. Tumor assessment was performed every 8 weeks per RECIST v1.1 assessed by investigator.

Results

As of data cut-off (April 12, 2023), 41 pts (median age 50 yrs [34-66], 61% ECOG PS 1) were enrolled. Median follow-up was 8.2 months (mo). Treatment-related adverse events (TRAEs) of ≥ Grade 3 were reported in 48.8% (20/41) of pts. The most common ≥ Grade 3 TRAEs (≥ 5%) were neutrophil count decreased (36.6%), white blood cell count decreased (22%), anemia (14.6%), platelet count decreased (9.8%) and GGT increase (7.3%). TRAEs led to dose reduction in 17.1% (7/41) of pts. No neuropathy or drug-related ILD/pneumonitis was reported. No TRAEs led to treatment discontinuation or death. Of 38 pts evaluable for response assessment, 47% of pts had primary endocrine resistance; 79% of pts had received ≥2 prior chemotherapy for metastatic disease, and prior treatments included taxane (100%), and CDK 4/6 inhibitors (65.8%). The ORR was 36.8% (14/38, 12 confirmed PR and 2 unconfirmed PR) and DCR was 89.5%, median DoR was 7.4 mo (range, 4.2 to 14.9+), 6-mo DoR rate was 80%. Median PFS was 11.1 mo (95% Cl: 5.4, 13.1), and 6-mo PFS rate was 61.2%.

Conclusions

SKB264 at 5 mg/kg demonstrates a manageable safety profile and promising antitumor activity in pts with pre-treated HR+/HER2- mBC. Two phase 3 studies are currently planned in HR+/HER2- mBC, one in China for pts after at least one chemo for mBC and a second global for pts previously untreated with chemo for mBC, both comparing SKB264 vs investigator selected chemo.

Clinical trial identification

NCT04152499.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Funding

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

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.