Sacituzumab tirumotecan (sac-TMT) in combination with tagitanlimab (anti-PD-L1) in first-line (1L) advanced non-small-cell lung cancer (NSCLC): Non-squamous cohort from the phase II OptiTROP-Lung01 study.

Abstract

8529 Background: Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor. The complementary mechanisms of action of sac-TMT and PD-1/L1 inhibitor may provide more potent antitumor activity. Sac-TMT was safety combined with tagitanlimab (anti-PD-L1, KL-A167) and demonstrated promising activity for the combination in 1L NSCLC ( Fang et al. 2024 ). Here, we report updated results by PD-L1 expression with additional enrolled patients (pts) and extended follow-up from non-squamous cohort in the phase II OptiTROP-Lung01 study (NCT05351788). Methods: Advanced NSCLC pts with no prior systemic therapy and no actionable genomic alterations were enrolled to receive sac-TMT (5 mg/kg Q3W or Q2W) plus tagitanlimab (1200 mg Q3W or 900 mg Q2W) until disease progression or unacceptable toxicity. Tumor assessments per RECIST 1.1 were performed once every 6 weeks for the first 12 months (mo), and every 12 weeks thereafter. The PD-L1 tumor proportion score (TPS) was detected by IHC 22C3 pharmDx assay. Results: As of 30 Dec 2024, 81 pts (median age: 60.0 years; male: 79.0%; ECOG PS 1: 91.4%) with non-squamous histology were enrolled. The majority (66.7%) had PD-L1 TPS< 50% (42.0% for < 1%, 24.7% for 1% - 49% and 33.3% for ≥ 50%). After median follow-up of 17.1 mo, the confirmed objective response rate (ORR) was 59.3%; The disease control rate (DCR) was 91.4%; Median duration of response (mDOR) was 16.5 mo (95%CI: 11.7, 22.1); Median progression free survival (mPFS) was 15.0 mo (95%CI: 10.8, 24.8). Among pts with PD-L1 TPS< 1%, the confirmed ORR was 47.1%; mPFS was 12.4 mo (95%CI: 7.6, 15.4); while for pts with PD-L1 TPS≥ 1%, the confirmed ORR was 68.1%; mPFS was 17.8 mo (95%CI: 14.5, NE). Among pts with PD-L1 TPS≥ 50%, the confirmed ORR was 77.8%; mPFS was 17.8 mo (95%CI: 10.8, NE). Most common (≥ 10%) Grade ≥ 3 treatment-related adverse events (TRAEs) were neutrophil count decreased (45.7%), anemia (16.0%), white blood cell count decreased (14.8%) and stomatitis (11.1%). No TRAE led to treatment discontinuation or death. Conclusions: Sac-TMT in combination with tagitanlimab demonstrated promising antitumor activity in treatment-naive advanced non-squamous NSCLC. The durable clinical activities were observed regardless of PD-L1 expression. This combination therapy showed a tolerable safety profile based on known profiles of the individual agents, with no new safety signals observed. A phase 3 study comparing sac-TMT plus pembrolizumab vs. chemotherapy plus pembrolizumab as 1L treatment for PD-L1 negative pts with advanced non-squamous NSCLC is ongoing (NCT06711900). Clinical trial information: NCT05351788 .