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Dr Krop on the Efficacy and Tolerability of SHR-A1811 in Advanced HER2+ Breast Cancer

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Ian Krop, MD, PhD, discusses SHR-A1811, a third-generation antibody-drug conjugate for HER2-positive breast cancer.

“SHR A1811…showed fairly remarkable activity with a very high [objective] response rate [at 79.1%] and a [median] progression-free survival of 20 months in this pretreated population. That looked quite encouraging compared [with] what's been seen with some of the other second-generation antibody-drug conjugates.”

Ian Krop, MD, PhD, director, Clinical Trials Office, chief clinical research officer, and associate director, Clinical Sciences, Yale Cancer Center, discusses findings from a phase 1 trial (NCT04446260) evaluating SHR-A1811, a third-generation antibody-drug conjugate (ADC), in the treatment of patients with HER2-positive breast cancer.

The study is examining the ADC in heavily pretreated patients with advanced breast cancer or other HER2-expressing solid tumors.

Findings presented at the 2024 San Antonio Breast Cancer Symposium showed that response-evaluable patients with HER2-positive breast cancer (n = 136) experienced an objective response rate (ORR) of 79.1% (95% CI, 71.2%-85.6%); the ORR was 62.0% (95% CI, 52.2%-71.2%) in patients with HER2-low breast cancer (n = 110) and 40.0% (95% CI, 31.5%-49.0%) in patients with non-breast solid tumors. The median progression-free survival (PFS) was 20.0 months (95% CI, 15.1-not evaluable) in the HER2-positive breast cancer population, 11.0 months (95% CI, 8.2-13.7) in the HER2-low breast cancer, cohort and ranged from 3.4 to 8.5 months in non–breast cancer cohorts.

The median duration of response (DOR) was 23.6 months (95% CI, 15.6-NE) for those with HER2-positive breast cancer, 12.2 months (95% CI, 7.3-NE) for patients with HER2-low breast cancer, and 15.2 months (95% CI, 9.9–20.9) in patients with non-breast tumors. In patients with liver or visceral metastases, the PFS and DOR data were consistent with the overall breast cancer population.

SHR-A1811 demonstrated a manageable safety profile with no new safety signals identified across the studied cohorts. Grade 3 treatment-related adverse effects (TRAEs) were reported in 63.2% of patients, and 6.6% of patients discontinued treatment due to TRAEs.

SHR-A1811 targets HER2 and carries a topoisomerase I inhibitor payload, Krop notes. He added that rates of interstitial lung disease with SHR-A1811 were lower than what would be expected with another ADC such as fam-trastuzumab deruxtecan-nxki (Enhertu). In the phase 1 trial, ILD occurred in 2.6% of all patients, and no grade 3 or higher ILD was reported. These data show SHR-A1811 could be a potential treatment option for patients with advanced HER2-positive breast cancer, he concludes.

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