Sacituzumab tirumotecan (SKB264/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study.

• DOI: 10.1200/jco.2024.42.16_suppl.8502
• Publication Date: 2024-06-26T16:57:38Z
• Authors: Wenfeng Fang; Qiming Wang; Ying Cheng; Yongzhong Luo; Xiujuan Qu; Haibo Zhu; Zhenyu Ding; XingYa Li; Lin Wu; Yan Wang; Sheng Hu; Enwen Wang; Anwen Liu; Yuping Sun; Yun Fan; Feng Ye; Kaihua Lu; Yalan Yang; Junyou Ge; Li Zhang
• Keywords: Second line

8502 Background: Sacituzumab Tirumotecan (SKB264/MK-2870)is a TROP2 ADC developed with novel linker to conjugate the payload, belotecan-derivative topoisomerase I inhibitor. The hydrolytically permits both extracellular pH-sensitive cleavage and intracellular enzymatic release membrane permeable payload enabling “bystander effect”. Here, we report initial results from phase II study of SKB264 combined KL-A167 in patients (pts) advanced NSCLC (OptiTROP-Lung01, NCT05351788). Methods: Pts treatment naive without actionable genomic alterations were enrolled receive 5 mg/kg Q3W + 1200 mg (cohort 1A) or Q2W 900 1B) non-randomized manner until disease progression unacceptable toxicity. Tumor assessments based on RECIST 1.1 performed every 6 weeks by investigators. Results: As 02 Jan 2024, 40 63 pts have been cohort 1A 1B. Median ages 63/63 years; 97.5%/85.7% had ECOG PS 1; 30.0%/33.3%, 32.5%/30.2% 37.5%/36.5% PD-L1 expression < 1%, 1%–49% ≥ 50% tumor cells IHC 22C3 pharmDx assay, respectively. In cohorts 1A/1B, most common Grade 3 treatment-related adverse events (TRAEs) neutrophil count decreased (30.0%/30.2%), white blood cell (5.0%/17.5%), anemia (5.0%/15.9%), rash (5.0%/6.3%) drug eruption (7.5%/0). TRAE leading discontinuation occurred 1 pt 1B due hypersensitivity, there no deaths. After median follow up 14.0 mos 6.9 for 1B, ORR was 48.6% (18/37, 2 pending confirmation), DCR 94.6% PFS 15.4 (95% CI: 6.7, NE) 6-mo rate 69.2% ; 77.6% (45/58, 100% not reached 84.6% Additional subgroup analyses are shown Table. Conclusions: combination demonstrated promising efficacy manageable safety profile. recommended further investigation. A Phase plus pembrolizumab vs 1L metastatic TPS (NCT06170788) is ongoing. Clinical trial information: NCT05351788 . [Table: see text]