The addition of the TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) to pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) vs pembrolizumab plus platinum-based chemotherapy in the first-line treatment of patients with PD-L1–negative, locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 OptiTROP-Lung06 trial (NCT06711900) at a prespecified interim analysis.1
At the prespecified interim analysis, the improvement in PFS by blinded independent central review (BICR) was statistically significant and clinically meaningful compared with pembrolizumab plus pemetrexed and platinum-based chemotherapy, and a positive trend in overall survival (OS) was also observed.
In a news release, Kelun-Biotech—the developer of sac-TMT—noted that this is the first phase 3 study of an ADC combined with an immune checkpoint inhibitor to meet its primary end point in the first-line treatment of patients with driver gene–negative, PD-L1–negative nonsquamous NSCLC.
The safety profile of sac-TMT plus pembrolizumab was consistent with that observed in previously reported studies of the ADC, and no new safety signals were identified. Kelun-Biotech plans to communicate these results with the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA).
“The achievement of positive results in the phase 3 OptiTROP-Lung06 study represents an important breakthrough in the first-line treatment of PD-L1–negative NSCLC. These results not only provide robust clinical evidence supporting the ‘ADC plus immunotherapy’ strategy of sac-TMT in combination with pembrolizumab, but also have the potential to offer these patients a new first-line treatment option beyond the current standard of care, with the promise of improved survival outcomes,” Caicun Zhou, of Shanghai East Hospital, Tongji University, in Shanghai, China, stated in the news release.
Zhou served as the national lead principal investigator for the study.
OptiTROP-Lung06 was a randomized, open-label, multicenter phase 3 study evaluating sac-TMT plus pembrolizumab vs chemotherapy plus pembrolizumab as first-line treatment for patients with locally advanced or metastatic nonsquamous NSCLC who have a PD-L1 tumor proportion score (TPS) of less than 1%.1,2 The study was conducted exclusively in China.2
Patients could not have disease harboring driver alterations, such as EGFR mutations and ALK fusions, and no prior treatment in the locally advanced or metastatic settings was permitted. Patients also needed to have at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 to 1, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function. Patients with tumors featuring a small cell component were excluded.
Investigators randomly assigned patients in a 1:1 fashion to receive sac-TMT on days 1, 15, and 29 of each 6-week cycle, plus pembrolizumab on day 1 of each cycle; or pembrolizumab on day 1 of each cycle plus pemetrexed and cisplatin/carboplatin on days 1 and 22.
Along with the primary end point of PFS per BICR, secondary end points included OS, investigator-assessed PFS, objective response rate, disease control rate, duration of response, time to response, and safety.
The OptiTROP-Lung06 readout follows
In that trial, the combination reduced the risk of disease progression or death by 65% vs pembrolizumab alone (HR, 0.35; 95% CI, 0.26-0.47; P < .0001); the median PFS by BICR was not reached (95% CI, 13.6-not evaluable) with the combination (n = 208) vs 5.7 months (95% CI, 4.3-7.0) with monotherapy (n = 205) at a median follow-up of 10.5 months.
Sac-TMT is being evaluated in 10 registrational studies in lung cancer, including 5 registrational studies in China and 5 global multicenter phase 3 studies, according to Kelun-Biotech.1
A new indication application for sac-TMT plus pembrolizumab as first-line treatment for patients with locally advanced or metastatic NSCLC who have a PD-L1 TPS of at least 1% and are EGFR-negative and ALK-negative has been accepted for review by the NMPA and entered the priority review and approval process.
