Sacituzumab Tirumotecan NDA for EGFR+ NSCLC Under Review in China

The National Medical Products Administration’s Center for Drug Evaluation has accepted for review a new drug application (NDA) seeking the approval of sacituzumab tirumotecan (formerly SKB264/MK-2870; sac-TMT) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations.¹

The NDA is supported by findings from a prespecified analysis of the phase 3 OptiTROP-Lung03 study in which the monotherapy, administered at 5 mg/kg every other week, provided a statistically significant and clinically meaningful improvement in objective response rate (ORR) and progression-free survival (PFS) vs docetaxel. Notably, these patients had progressed on treatment with an EGFR TKI and platinum-based chemotherapy.

“It is a great honor to have the second NDA of SKB264 accepted. Kelun-Biotech has always adhered to an innovation-driven development strategy, actively exploring cutting-edge technologies and new approaches to the treatment of major diseases. In response to unmet medical needs, we are committed to the original innovation of new drugs with differentiated advantages and international potential,” Junyou Ge, PhD, director of the National Engineering Research Center for Biotargeted Drugs and chief executive officer of Kelun-Biotech, stated in a news release. “By enhancing our end-to-end innovative drug development capabilities, we continuously improve the efficiency and success rate of drug research and development and make every effort to move forward our clinical research progress. We are dedicated to continuously exploring and rapidly validating the clinical value of core projects. The company will always be guided by a caring heart, striving for excellence, and contributing to the great global oncology health cause.”

Data from the phase 2 OptiTROP-Lung01 study (NCT05351788) were presented at the 2024 ASCO Annual Meeting.² When the TROP2-targeted antibody-drug conjugate was administered at 5 mg/kg every 3 weeks and paired with the anti–PD-L1 monoclonal antibody KL-A167 given at 1200 mg every 3 weeks (cohort 1a; n = 40), it resulted in an ORR of 48.6% (95% CI, 31.9%-65.6%) in patients with locally recurrent or metastatic NSCLC who had not received prior systemic therapy. The median duration of response was not yet reached (NR; 95% CI, 8.3-not evaluable [NE]), and the disease control rate 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 a dose of 900 mg every 2 weeks (cohort 1b; n = 63), the ORR was higher, at 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 PFS rate at 6 months was 84.6% (95% CI, 71.4%-92.1%).

Additional analyses of cohort 1b, those who received treatment every 2 weeks, revealed that clinical benefits were observed in all PD-L1 expression and histology subgroups. 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%).

Regarding safety, treatment-related adverse effects (TRAEs) were experienced by 95% of those in cohort 1A and 96.8% of those in cohort 1b; these effects were grade 3 or higher for 42.5% and 54.0% of patients, 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. Treatment-related serious adverse effects were experienced by 10% of those in cohort 1a and 22.2% of those in cohort 1b. No TRAEs proved to be fatal.

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

Phase 3 studies are evaluating the safety and efficacy of sac-TMT plus pembrolizumab (Keytruda) in patients with NSCLC. One trial (NCT06170788) is evaluating the combination as first-line treatment for those with a PD-L1 TPS of 50% or higher, another (NCT06422143) is evaluating the regimen as maintenance treatment in those with metastatic squamous disease, and the third (NCT06312137) is examining the combination as post-operative treatment in those with resectable disease who did not achieve a pathologic complete response.

Previously, the NMPA accepted for review another NDA seeking the approval of sac-TMT for use in patients with locally advanced or metastatic triple-negative breast cancer who have previously received at least 2 systemic therapies, at least 1 of which in the advanced or metastatic setting.¹

References

1. Kelun-Biotech’s TROP2-ADC SKB264 (sac-TMT) second NDA accepted by NPMA, locally advanced or metastatic EGFR-mutant NSCLC. News release. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. August 20, 2024. Accessed August 20, 2024. https://en.kelun-biotech.com/newsCenter.aspx?mid=18
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