The National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) in China has accepted a new drug application (NDA) for sacituzumab tirumotecan (sac-TMT), formerly known as SKB264/MK-2870, for treating adult patients with EGFR-mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed following EGFR TKI treatment. The NMPA's CDE intends to include this NDA in the priority review and approval process.
The application is supported by positive results from the pivotal phase 3 OptiTROP-Lung04 study, a multicenter, randomized trial evaluating sac-TMT monotherapy versus pemetrexed plus platinum-based chemotherapy in patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after EGFR TKI therapy.
Interim analysis of the OptiTROP-Lung04 data demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with sac-TMT monotherapy compared to pemetrexed plus platinum chemotherapy, as assessed by the blinded independent review committee. The safety profile of sac-TMT was manageable, with no unexpected safety signals identified.
"Sacituzumab govitecan has received its third NDA," said Junyou (Michael) Ge, PhD, director of the National Engineering Research Center for Biotargeted Drugs, director, and chief executive officer of Kelun-Biotech, in a news release. "We believe that sac-TMT will shine in the field of oncology and contribute Chinese strength to the global health cause."
Mechanism of Action and Prior Studies
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. The ADC 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.
Upon binding, the ADC is internalized by tumor cells, releasing the payload KL610023 intracellularly. KL610023, a topoisomerase I inhibitor, induces DNA damage within tumor cells, leading to cell-cycle arrest and apoptosis. Additionally, KL610023 is released into the tumor microenvironment, where its membrane-permeable properties enable a bystander effect, effectively killing nearby tumor cells.
Sac-TMT monotherapy was previously assessed in the phase 2 OptiTROP-Lung01 study (NCT05351788), with results presented at the 2024 ASCO Annual Meeting. Furthermore, the phase 3 OptiTROP-Lung03 trial demonstrated a statistically significant and clinically meaningful improvement in objective response rate and PFS with sac-TMT compared to docetaxel in patients with locally advanced or metastatic NSCLC harboring EGFR mutations.
Prior to this application, the NMPA accepted two NDAs for sac-TMT: one for patients with locally advanced or metastatic triple-negative breast cancer who have received at least two prior systemic therapies, and another for patients with locally advanced or metastatic EGFR-mutant NSCLC who experienced progression following treatment with an EGFR-TKI and platinum-based chemotherapy.
