Abstract 329P
Background
Currently, it’s still an urgent unmet clinical need for systemic treatment that also had excellent CNS anti-tumor activity in lung cancer, especially in SCLC. YL201 is a B7-H3-targeting ADC which has shown promising clinical activity in multiple advanced solid tumors. Here, we report the exploratory analysis of intracranial antitumor activity of YL201 in pts with SCLC and NSCLC from phase I study.
Methods
Pts with extensive-stage SCLC or locally advanced/metastatic wild-type (WT) NSCLC who had received ≥1 prior systemic therapies were treated with YL201 intravenously Q3W. Pts with stable (asymptomatic and without steroids) CNS metastases (treated or untreated) were eligible. Intracranial responses were assessed by investigators per RECIST 1.1 at baseline, every 6 weeks to Week 24, and every 9 weeks thereafter.
Results
A total of 29 pts had CNS metastasis at baseline (SCLC n=21; WT NSCLC n=8), including 13 pts (SCLC n=10; WT NSCLC n=3) with ≥1 CNS target lesions. Pts with baseline CNS metastasis had a median (range) of 1 (1–5) prior systemic therapies in the advanced setting. At the data cutoff, the median intracranial median progression-free survival was 6.2 months (95% CI: 3.9–NR). In pts with target lesions, the intracranial objective response rate (ic-ORR) and disease control rate (ic-DCR)were 30.8% and 100.0%, respectively. The ic-ORR and ic-DCR were 57.1% and 100.0% in the subset of pts without prior CNS RT or with prior CNS RT ≥6 months before the start of study (Table). Among all patients enrolled in the study, 0.9% reported treatment-related Grade ≥3 CNS disorder.
Table 329P| Pts with brain target lesion | Subset of pts without prior CNS RT or with prior CNS RT ≥6 months before start | |||||
| SCLC (N=10) | WT NSCLC (N=3) | Total (N=13) | SCLC (N=6) | WT NSCLC (N=1) | Total (N=7) | |
| ic-ORR (%) | 30.0 | 33.3 | 30.8 | 50.0 | 100.0 | 57.1 |
| 95% CI | 6.7–65.3 | 0.8–90.6 | 9.1–61.4 | 11.8–88.2 | 2.5–100 | 18.4–90.1 |
| ic-DCR (%) | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
| 95% CI | 69.2–100 | 29.2–100 | 75.3–100 | 54.1–100 | 2.5–100 | 59.0–100 |
Conclusions
YL201 shows durable intracranial antitumor activity in SCLC and WT NSCLC pts with CNS metastasis at baseline, supporting further investigation of YL201 in these pts.
Clinical trial identification
NCT05434234 & NCT06057922.
Legal entity responsible for the study
The authors.
Funding
MediLink Therapeutics (Suzhou) Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.