276P - SHR-A1811 in combination with pyrotinib as neoadjuvant treatment for HER2-positive breast cancer (HER2+ BC): Preliminary results from MUKDEN 07

Background

Significant though the advances in neoadjuvant anti-HER2 therapies have been, achieving higher cure rates remains an unmet need in HER2+ BC. SHR-A1811, a novel anti-HER2 ADC, has shown promising antitumor activity in metastatic HER2+ BC. This study (NCT05635487) evaluated varying doses of SHR-A1811 combined with pyrotinib, a pan-ErbB inhibitor, as neoadjuvant therapy in patients (pts) with HER2+ BC.

Methods

Eligible women aged 18-75 with newly diagnosed stage II-III, untreated HER2+ BC received SHR-A1811 Q3W and daily pyrotinib for six cycles. Initial treatment was SHR-A1811 at 4.8 mg/kg and pyrotinib at 240 mg/day (Cohort A). Dose adjustments followed the 3+3 principle: If tolerated, SHR-A1811 could escalate to 5.6 mg/kg, maintaining pyrotinib (Cohort B). For intolerance or investigator discretion, adjustments included SHR-A1811 at 4.8 mg/kg with pyrotinib at 160 mg/day (Cohort C), or SHR-A1811 at 4.0 mg/kg with pyrotinib at 240 mg/day (Cohort D). Primary endpoint: pathological complete response (tpCR: ypT0-is/ypN0). Secondary endpoints: breast pathological complete response (bpCR: ypT0-is), residual cancer burden (RCB), objective response rate (ORR), safety, and dose-limiting toxicities (DLTs).

Results

As of Nov 14, 2023, 29 pts were enrolled (8 in A; 4 in B; 10 in C; 7 in D): median age, 55 years (range 38-61); T2 (89.7%); nodal involvement (62.1%); and stage IIB-III (65.5%). The overall tpCR rate was 78.6% (22/28, 95% CI, 59.1-91.7), with rates of 75.0% in A, 66.7% in B, 70.0% in C, and 100% in D. The tpCR rates for HR+ and HR- populations were 76.5% (13/17, 95% CI, 50.1-93.2) and 81.8% (9/11, 95% CI, 48.2-97.7), respectively. BpCR results were consistent with tpCR. RCB-0/I was 89.3% (25/28, 95% CI, 71.8–97.7). The ORR was 89.7%, with rates of 100% in A, 75.0% in B, 90.0% in C, and 85.7% in D. Four pts experienced DLTs, including diarrhea (A/C), neutropenia (B), and thrombocytopenia (D). The most common Grade 3/4 treatment-related adverse events were neutropenia (62.1%), diarrhea (51.7%), leukopenia (44.8%), hypokalemia (24.1%) and anaemia (20.7%).

Conclusions

SHR-A1811 combined with pyrotinib as neoadjuvant therapy for HER2+ BC yields promising antitumor efficacy with manageable toxicity.

Clinical trial identification

NCT05635487.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.