In a Chinese phase I trial reported in The Lancet Oncology, Ma et al found that BL-B01D1—a first-in-class EGFR-HER3 bispecific antibody-drug conjugate—was active in previously treated patients with locally advanced or metastatic solid tumors.
Study Details
In the multicenter trial, 195 patients were enrolled between December 2021 and March 2023, including 25 in phase Ia (dose escalation) and 170 in phase Ib (dose expansion). The most common cancers in the cohort were non–small cell lung cancer (n = 113) and nasopharyngeal carcinoma (n = 42). A total of 50% of patients had received at least three prior lines of treatment.
Key Findings
Testing of multiple dose levels in phase I showed four dose-limiting toxicities (all febrile neutropenia) at 3.0 mg/kg weekly (n = 2) and 3.5 mg/kg on days 1 and 8 every 3 weeks (n = 2). The maximum tolerated doses were determined to be 3.0 mg/kg on days 1 and 8 every 3 weeks and 6.0 mg/kg on day 1 every 3 weeks.
In phase Ib, patients received BL-B01D1 at 2.5 and 3.0 mg/kg on days 1 and 8 every 3 weeks or 4.5, 5.0, and 6.0 mg/kg on day 1 every 3 weeks. Among 174 patients evaluable for efficacy, confirmed objective responses (all partial responses) were observed in 60 (34%, 95% confidence interval [CI] = 27%–42%). A total of 80 patients (46%) had confirmed partial response or partial response pending confirmation. The disease control rate was 89%. Median duration of response was 8.5 months (95% CI = 5.4 months to not evaluable). The dose recommended for phase II testing was 2.5 mg/kg on days 1 and 8 every 3 weeks.
Among all 195 patients, grade ≥ 3 treatment-related adverse events occurred in 139 (71%), most commonly neutropenia (47%), anemia (39%), leukopenia (39%), and thrombocytopenia (32%). Treatment-related adverse events resulted in discontinuation of treatment in five patients (3%). Treatment-related death occurred in three patients (2%), due to pneumonia, septic shock, and myelosuppression, respectively.
The investigators concluded, “Our results suggest that BL-B01D1 has preliminary antitumor activity in [patients with] extensively and heavily treated advanced solid tumors with an acceptable safety profile. Based on the safety and antitumor activity data from both phase Ia and Ib, 2.5 mg/kg on days 1 and 8 every 3 weeks was selected as the recommended phase II dose in Chinese patients.”
Li Zhang, MD, of the Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Sichuan Baili Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.
