Sacituzumab Tirumotecan NDA for Pretreated EGFR+ NSCLC Accepted for Review in China

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

This marks the third NDA submission for sacituzumab tirumotecan that has been accepted by the regulatory agency. The NMPA’s CDE announced the intention for this NDA to be included in the priority review and approval process on October 25, 2024.

The application was supported by positive results from the pivotal phase 3 OptiTROP-Lung04 study. This multicenter, randomized, registrational study is evaluating the efficacy and safety of sac-TMT monotherapy vs pemetrexed plus platinum-based chemotherapy for patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after treatment with EGFR TKI therapy.

Prespecified interim analysis of the data showed that treatment with sac-TMT monotherapy produced statistically significant and clinically meaningful improvement in the study’s primary end point of progression-free survival (PFS) as assessed by the blinded independent review committee compared with pemetrexed plus platinum chemotherapy. Sac-TMT also displayed a manageable safety profile, with no unexpected safety signals identified.

"Sacituzumab govitecan has received its third NDA," Junyou (Michael) Ge, PhD , director of the National Engineering Research Center for Biotargeted Drugs, director, and chief executive officer of Kelun-Biotech, stated in a news release. "In response to unmet clinical needs, the company has always adhered to the spirit of hard work inherent in Kelun, focusing on original innovation and doing practical work to develop new drugs with differentiated advantages and international potential. We believe that sac-TMT will shine in the field of oncology and contribute Chinese strength to the global health cause."

Prior Data and Applications for Sacituzumab Tirumotecan

Sac-TMT is a novel antibody-drug conjugate (ADC) targeting human TROP2 in advanced solid tumors including NSCLC, breast cancer, gastric cancer, and gynecological tumors.¹ The agent utilizes a novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor payload, designed with a drug-to-antibody ratio of 7.4. Sac-TMT binds to TROP2 on the surface of tumor cells using recombinant anti-TROP2 humanized monoclonal antibodies.

Once bound, the ADC is internalized by tumor cells, where it releases the payload KL610023 intracellularly. KL610023, acting as a topoisomerase I inhibitor, initiates DNA damage within tumor cells, resulting in cell-cycle arrest and apoptosis. Additionally, KL610023 is also released into the tumor microenvironment, where its membrane-permeable properties enable a bystander effect, effectively killing nearby tumor cells.

Sac-TMT monotherapy was previously evaluated in the phase 2 OptiTROP-Lung01 study (NCT05351788), results from which were presented at the 2024 ASCO Annual Meeting.² Additionally, results from the phase 3 OptiTROP-Lung03 trial demonstrated a statistically significant and clinically meaningful improvement in objective response rate and PFS with sac-TMT vs docetaxel for patients with locally advanced or metastatic NSCLC harboring EGFR mutations.³

In addition to the current application, the NMPA previously accepted 2 NDAs for sac-TMT for patients with locally advanced or metastatic triple-negative breast cancer who have received at least 2 prior systemic therapies—including 1 or more therapies in the advanced or metastatic setting—and for those with locally advanced or metastatic EGFR-mutant NSCLC who experienced progression following treatment with an EGFR-TKI and platinum-based chemotherapy, respectively.¹

Additionally, the company noted the licensing of exclusive rights to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China, including Mainland China, Hong Kong, Macao, and Taiwan.

References

1. Kelun-Biotech's TROP2-ADC SKB264 (sac-TMT) Third NDA Accepted by NMPA, locally advanced or metastatic EGFR-mutant NSCLC. News release. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. October 31, 2024. Accessed October 31, 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
3. 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 October 31, 2024. https://en.kelun-biotech.com/newsCenter.aspx?mid=18