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.

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