China’s NMPA Approves Sacituzumab Tirumotecan for Pretreated EGFR+ Advanced NSCLC

The Chinese National Medical Products Administration (NMPA) has granted marketing authorization to the TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; formerly SKB264/MK-2870) for the treatment of adult patients with EGFR-mutant locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) following disease progression on an EGFR TKI and platinum-based chemotherapy.1

The approval is supported by findings from the phase 2 OptiTROP-Lung03 trial, a randomized, controlled, multicenter pivotal study evaluating sac-TMT monotherapy at 5 mg/kg every other week vs docetaxel in patients with previously treated, locally advanced or metastatic EGFR-mutant NSCLC. Findings from a prespecified interim analysis of the study showed that patients treated with sac-TMT experienced statistically significant and clinically meaningful improvements in objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) vs those treated with docetaxel.

"We are very pleased that the second indication of…sac-TMT has been approved for marketing, which is exciting progress for us in the field of lung cancer. The successful approval of this new indication will help to address an unmet treatment need for patients with later-stage EGFR-mutant NSCLC in China," Michael Ge, MD, chief executive officer of Kelun-Biotech, stated in a news release.

Previously, in November 2024, the NMPA approved sac-TMT for adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least 2 prior systemic therapies, including at least 1 in the advanced or metastatic setting. Additionally, the regulatory agency previously accepted a supplemental new drug application seeking the approval of sac-TMT as monotherapy for patients with EGFR-mutant NSCLC who progressed after an EGFR TKI.

Data from the phase 2 OptiTROP-Lung01 study (NCT05351788), which were presented at the 2024 ASCO Annual Meeting, evaluated sac-TMT in combination with the anti–PD-L1 monoclonal antibody KL-A167 in patients with locally recurrent or metastatic NSCLC harboring no actionable mutations/alterations who received no prior systemic therapy and had an ECOG performance status of 0 or 1.2

In cohort 1a (n = 40), where sac-TMT was given at 5 mg/kg once every 3 weeks in combination with KL-A167 at 1200 mg every 3 weeks, the overall response rate (ORR) was 48.6% (95% CI, 31.9%-65.6%).

At the time of analysis, the median duration of response (DOR) for cohort 1a was not reached (NR; 95% CI, 8.3-not evaluable [NE]), and the disease control rate (DCR) was 94.6%. The median PFS was 15.4 months (95% CI, 6.7-NE) with a 6-month PFS rate of 69.2% (95% CI, 51.2%-81.6%).

When sac-TMT was given at a dose of 5 mg/kg every 2 weeks plus KL-A167 at 900 mg every 2 weeks (cohort 1b; n = 63), the ORR was 77.6% (95% CI, 64.7%-87.5%). The median DOR was NR (95% CI, 6.6-NE) and the DCR was 100%. The median PFS was NR (95% CI, 8.4-NE), and the 6-month PFS rate was 84.6% (95% CI, 71.4%-92.1%).

OptiTROP-Lung01 Data Deep Dive

Further analyses of cohort 1b, revealed that clinical benefits were observed irrespective of PD-L1 expression and histology. In those with a PD-L1 tumor proportion score (TPS) under 1% (n = 21), the ORR was 63.2%, the DCR was 100%, and the 6-month PFS rate was 82.2% (95% CI, 54.3%-93.9%).

In the group of patients with a PD-L1 TPS ranging from 1% to 49% (n = 19), the ORR, DCR, and 6-month PFS rate was 81.3%, 100%, and 76.6% (95% CI, 41.2%-92.3%), respectively. In those with a PD-L1 TPS of at least 50% (n = 23), these respective rates were 87%, 100%, and 91.3% (95% CI, 69.5%-97.8%).

In those with nonsquamous histology (n = 34), the ORR was 72.7%, the DCR was 100%, and the PFS rate at 6 months was 93.8% (95% CI, 77.3%-98.4%). In those with squamous histology (n = 29), these respective rates were 84%, 100%, and 73.5% (95% CI, 49.9%-87.2%).

Safety Analysis

Regarding safety, treatment-related adverse effects (TRAEs) were experienced by 95% of patients in cohort 1A and 96.8% of those in cohort 1b; rates of grade 3 or higher TRAES were 42.5% and 54.0%, respectively. In cohort 1a, TRAEs led to dose reductions or interruptions for 17.5% and 25% of patients, respectively; in cohort 1b, these respective rates were 31.7% and 50.8%. TRAEs led to the discontinuation of any drug for 1 patient in cohort 1a and 2 patients in cohort 1b.

Serious TRAEs were experienced by 10% of those in cohort 1a and 22.2% of those in cohort 1b. No TRAEs led to death.

The most common TRAEs experienced by 20% or more of patients were anemia, decreased neutrophil count, decreased white blood cell count, alopecia, rash, nausea, reduced appetite, increased alanine aminotransferase level, stomatitis, increased aspartate aminotransferase level, decreased platelet count, and fatigue. Grade 2 interstitial lung disease was reported in 1 patient in cohort 1b.

References

1. Kelun-Biotech’s TROP2 ADC sacituzumab tirumotecan (sac-TMT) approved for marketing in second indication by NMPA for EGFRm NSCLC. Kelun-Biotech. March 10, 2025. Accessed March 10, 2025. https://www.prnewswire.com/news-releases/kelun-biotechs-trop2-adc-sacituzumab-tirumotecan-sac-tmt-approved-for-marketing-in-second-indication-by-nmpa-for-egfrm-nsclc-302396917.html
2. Fang W, Wang Q, Cheng Y, et al. 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. J Clin Oncol. 2024;42(suppl 16):8502. doi:10.1200/JCO.2024.42.16_suppl.8502