Phase I study of BL-M14D1, a novel DLL3-directed antibody-drug conjugate (ADC), in patients with locally advanced or metastatic small-cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), and other solid tumors.
Year: 2026
Type: conference-abstract
Abstract: 3001 Background: BL-M14D1 is a novel DLL3-directed ADC with a potent topoisomerase I inhibitor Ed-04. Results for safety and efficacy from a phase I study on BL-M14D1 in patients with locally advanced or metastatic (LA/M) SCLC and NEC are presented. Methods: Patients who had LA/M solid tumors were enrolled in dose escalation and dose expansion phase and treated with BL-M14D1 at 0.66, 2.0, 3.5, 4.0, 4.5, 5.0, and 6.0mg/kg on Day 1 every 3 weeks (D1 Q3W). SCLC and NEC patients enrolled in dose expansion phase were treated at 4.0 and 4.5mg/kg D1 Q3W. Results: As of Nov 30, 2025, a total of 127 patients were enrolled, including 87 SCLC and 40 NEC. Median prior line of therapy was 2 (range 1-5). Treatment-related AEs (TRAEs) rate was 98.4% and grade≥3 TRAEs rate was 74.0%. The most frequent grade≥3 TRAEs were hematologic, including thrombocytopenia (54.3%), neutropenia (53.5%), leukopenia (46.5%) and anemia (32.3%), which were able to be effectively managed with standard supportive measures including dose reductions, as demonstrated by a low rate (1.6%) of TRAEs leading to discontinuation. One grade 3 ILD and one treatment-related death was reported. Efficacy data at 4.0 and 4.5mg/kg was presented below. BL-M14D1 has demonstrated a promising efficacy with an ORR/cORR of 71.1%/57.8% and mPFS of 7.2 months in heavily pre-treated SCLC. Furthermore, BL-M14D1 has shown encouraging activity in other gastrointestinal and gynecological NECs. Conclusions: BL-M14D1 has demonstrated promising antitumor activity with a tolerable safety profile at dose levels of 4.0mg/kg and 4.5mg/kg D1 Q3W in heavily pretreated patients with SCLC and NEC, supporting further clinical development of BL-M14D1 in SCLC and other less common NECs. Phase III studies assessing BL-M14D1 in SCLC and NEC are in preparation. Clinical trial information: NCT06505824 . SCLC Total * (N=83) SCLC 4.0mg/kg (N=34) SCLC 4.5mg/kg (N=37) NEC † Total * (N=22) NEC † 4.0mg/kg (N=3) NEC † 4.5mg/kg (N=19) Median prior LoT (range) 2 (1-5) 2 (1-3) 2 (1-5) 2 (1-3) 2 (1-2) 2 (1-3) ORR, % (95% CI) 71.1 (60.1, 80.5) 73.5 (55.6, 87.1) 70.3 (53.0, 84.1) 40.9 (20.7, 63.6) 33.3 (0.8, 90.6) 42.1 (20.3, 66.5) cORR, % (95% CI) 57.8 (46.5, 68.6) 61.8 (43.6, 77.8) 56.8 (39.5, 72.9) 27.3 (10.7, 50.2) 33.3 (0.8, 90.6) 26.3 (9.1, 51.2) DCR, % (95% CI) 94.0 (86.5, 98.0) 97.1 (84.7, 99.9) 91.9 (78.1, 98.3) 90.9 (70.8, 98.9) 100 (29.2, 100) 89.5 (66.9, 98.7) mFU for PFS (mo) (95% CI) 6.8 (5.5, 7.2) 7.7 (5.6, 8.2) 4.4 (4.1, 5.5) 3.0 (1.6, 4.3) NR (1.8, NR) 3.0 (1.4, 3.9) mPFS (mo) (95% CI) 7.2 (5.6, 12.7) 7.2 (5.6, NR) 6.9 (4.2, NR) 5.3 (3.9, NR) 4.6 (3.9, 5.3) NR (2.6, NR) † Sites of NEC included cervix, esophagus, stomach and others. * Efficacy analysis included pts at 4.0 and 4.5 mg/kg who received BL-M14D1 and had at least one post-baseline scan.
Source: Journal of Clinical Oncology
Institutions: Shanghai East Hospital, Shandong First Medical University, Fujian Provincial Cancer Hospital, Henan Medical University, Hunan Cancer Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Guilin Medical University, Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Peking University Cancer Hospital, Sichuan University, West China Hospital of Sichuan University, First Affiliated Hospital of Nanchang University, Guangxi Medical University, Tumor Hospital of Guangxi Medical University, First Hospital of Jilin University, Sichuan Baili Pharmaceutical Co., Ltd. (China)
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7162570890