KEY TAKEAWAYS
- The study aimed to assess the efficacy and safety of combining SKB264 with KL-A167 in patients with advanced NSCLC.
- Researchers observed that SKB264 + KL-A167 demonstrated promising efficacy and safety; further investigation is ongoing.
Sacituzumab Tirumotecan (SKB264/MK-2870) is a TROP2 ADC developed with a 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.” They reported the initial results from a phase II study of SKB264 combined with KL-A167 in patients with advanced Non Small Cell Lung Cancer (NSCLC) (OptiTROP-Lung01, NCT05351788).
Wenfeng Fang and the team aimed to assess the efficacy and safety of combining SKB264 with KL-A167 in treatment-naive advanced NSCLC.
They performed an inclusive analysis, enrolling patients with treatment-naive advanced NSCLC lacking actionable genomic alterations to receive either 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 conducted every 6 weeks by investigators.
As of Jan 02, 2024, 40 and 63 patients were enrolled in cohorts 1A and 1B. Median ages were 63 years; 97.5% and 85.7% had ECOG PS of 1. PD-L1 expression < 1%, 1%–49%, and ≥ 50% were observed in 30.0%, 32.5%, and 37.5% for cohort 1A, and 33.3%, 30.2%, and 36.5% for cohort 1B, respectively. In cohorts 1A and 1B, the most common Grade ≥ 3 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 patient of cohort 1B due to drug hypersensitivity, with no treatment-related deaths reported. After a median follow-up of 14.0 months and 6.9 months 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 months (95% CI: 6.7, NE) with a 6-month 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 a 6-month PFS rate of 84.6% for cohort 1B.
The study concluded that SKB264, in combination with KL-A167 showed promising efficacy and a manageable safety profile in treatment-naive advanced NSCLC. SKB264 Q2W was recommended for further investigation. Ongoing Phase 3 research comparing SKB264 Q2W plus pembrolizumab to pembrolizumab alone in first-line metastatic NSCLC with PD-L1 TPS ≥ 50% (NCT06170788) aims to provide further insights.
The study was sponsored by the Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Source: https://meetings.asco.org/abstracts-presentations/232877
Clinical Trial: https://clinicaltrials.gov/study/NCT05351788
Fang W, Wang Q, Cheng Y, et al. (2024). “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.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 16; abstr 8502), 10.1200/JCO.2024.42.16_suppl.8502.
