OptiTROP-Lung06 trial

Background

Phase 3, open-label, randomized (1:1). N=455 patients with untreated locally advanced/metastatic nonsquamous NSCLC without targetable genomic alterations and PD-L1 TPS <1%. Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed ADC. Prespecified interim analysis reported.

Results

Interventions and follow up: Arm A: sacituzumab tirumotecan + pembrolizumab (n=229)
Arm B: platinum-pemetrexed chemotherapy + pembrolizumab (n=226)
Primary endpoint: PFS by BICR
Secondary: OS
mFollow up: 9.7mo
Results: PFS: 15.0 vs 5.7mo, HR 0.49 (95% CI 0.36–0.65), P<.001
ORR: 50.2% vs 47.3%
Median DOR: 13.6 vs 6.8mo
OS: immature; HR 0.58 (95% CI 0.38–0.88)

Adverse events

Grade ≥3 (any): 47.6% vs 60.6%
Stomatitis: common with sac-TMT + pembrolizumab, predominantly grade 1–2
Other specifics / discontinuation: NR in abstract

Conclusions

First-line sac-TMT + pembrolizumab significantly prolonged PFS vs chemotherapy + pembrolizumab in PD-L1-negative nonsquamous NSCLC, with similar ORR but longer response duration and fewer grade ≥3 AEs. OS data immature.

Key Limitations

Interim analysis with only 9.7mo follow-up; OS immature (wide CI). Open-label. Conducted in China, so generalizability to other populations is uncertain. Similar ORR with durable benefit suggests effect on duration but long-term benefit unproven. Comparator is chemo-pembrolizumab; sac-TMT monotherapy or other ADC combinations not tested.

Clinical Context

Context: pembrolizumab + platinum-pemetrexed is a standard 1L option for PD-L1-negative nonsquamous NSCLC, with suboptimal outcomes. OptiTROP-Lung06 is the first randomized phase 3 of a TROP2 ADC + PD-1 in this setting. Regulatory status of sac-TMT outside China is not claimed here.

References