A phase II study to evaluate the safety and efficacy of BB-1701 in combination with sintilimab in patients with HER2 expression or mutation in locally advanced/metastatic breast cancer or NSCLC.

2632 Background: BB-1701, a HER2-targeting antibody-drug conjugate (ADC) containing eribulin, has demonstrated promising antitumor activity in the clinical studies in breast cancer (BC) patients with HER2 low expression and non-small cell lung cancer (NSCLC) patients with HER2 mutation. Currently, there are no approved treatment options of ADC in combination with anti-PD-1 antibody for metastatic BC patients with HER2 low expression and NSCLC patients with HER2 mutation. We report the preliminary efficacy and safety results from the ongoing phase 2 study (including dose escalation and dose expansion) of BB-1701 in combination with Sintilimab (an anti-PD-1 antibody) in advanced or metastatic BC patients with HER2 low expression and NSCLC patients with HER2 mutation. Methods: Patients enrolled were ≥18 years of age; had confirmed locally advanced/metastatic HER2 low-expressing BC or HER2 mutated NSCLC, an ECOG PS <2 and measurable lesion(s) (per RECIST v1.1); and disease progression after ≥1 lines of prior standard therapies. HER2 expression was confirmed by IHC or NGS/PCR before patient enrollment. BB-1701 was administered at 1.2 mg/kg Q3W or 1.6 mg/kg Q3W, and sintilimab is administered at 200 mg Q3W. Results: As of 26 January 2026, a total of 12 patients with HER2 low-expressing BC or HER2 mutated NSCLC have been enrolled and treated, 6 patients at each dose level of BB-1701 during dose escalation. Median age is 63 years, 91.7%/8.3% patients were female/male, and 16.7%/83.3% patients have ECOG PS 0/1. The median number of prior systemic therapy lines was 2.0/1.0 for BC and NSCLC. All patients experienced at least one treatment-emergent adverse events (TEAEs). The most common (≥20%) reported all grade TEAEs are alanine aminotransferase increased, aspartate aminotransferase increased, γ-glutamyltransferase increased, hypercholesterolemia, peripheral neuropathy, anemia and Urinary tract infection. Three grade 3 TEAEs are γ-glutamyltransferase increased, pneumonia and open globe injury. There has been no grade 4 or grade 5 events as of data cut-off date. One treatment emergent serious adverse event is open globe injury. All patients were evaluable for efficacy. Among 5 BC patients, 4 patients achieved partial response (PR) with disease control rate (DCR) of 80.0%. Among 7 NSCLC patients, 2 patients achieved PR and 2 patients had stable disease (SD) with DCR of 57.1%. Details of data will be presented at the ASCO meeting. Conclusions: BB-1701 in combination with Sintilimab shows encouraging antitumor activity and a manageable safety profile in HER2 low-expressing BC patients and HER2 mutated NSCLC patients. The further dose expansion study is guaranteed based on the preliminary data from dose escalation study. Clinical trial information: CTR20241422.