Kelun gets world-first approval for TROP2 ADC

Kelun-Biotech has picked up another first for its TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT), after getting Chinese approval of the drug in non-small cell lung cancer (NSCLC).

The National Medical Products Administration (NMPA) has cleared sac-TMT for patients with EGFR-mutant locally advanced or metastatic NSCLC whose disease has progressed after first-line EGFR tyrosine kinase inhibitor (TKI) treatment.

It is the third indication for the ADC and its second world-first for a TROP2 drug after sac-TMT got a green light from the NMPA for EGFR-mutated NSCLC previously treated with both an EGFR inhibitor and chemotherapy. Kelun's drug is also indicated in China as a third-line option for triple-negative breast cancer (TNBC).

Kelun said that sac-TMT "is the first and only ADC globally to show an overall survival (OS) benefit compared with platinum doublet chemotherapy and to be approved for advanced NSCLC that has progressed after only TKI therapy."

Its NMPA approval is based on the results of the OptiTROP-Lung04 study, which is due to be presented later this week at the ESMO cancer congress, showing improvements in both progression-free survival (PFS) and overall survival (OS).

It marks another victory for Kelun against some much larger rivals in the TROP2 ADC category, notably AstraZeneca/Daiichi Sankyo and Gilead Sciences.

AZ and Daiichi's Datroway (datopotamab deruxtecan) was finally approved in the US in June for third-line use after TKIs and chemotherapy in the US, after pulling its first marketing application.

In China, Datroway has only been approved to date for previously treated, advanced HR-positive, HER2-negative breast cancer – an indication currently under review at the NMPA for sac-TMT. Gilead's Trodelvy (sacituzumab govitecan), meanwhile, has been approved so far for previously treated TNBC only.

"We are delighted to announce the approval of the third indication for our core product, sac-TMT, marking another major milestone in lung cancer treatment," said Kelun's chief executive, Dr Michael Ge.

"EGFR mutations are the most common oncogenic driver in lung cancer, accounting for approximately 40%–50% of non-squamous NSCLC cases in China," he added. "Third-generation EGFR-TKIs are the standard first-line therapy for these patients, yet resistance inevitably develops, leaving few effective treatment options."

Kelun is also testing sac-TMT in combination with AZ's EGFR-TKI Tagrisso (osimertinib) for first-line treatment of EGFR-mutant NSCLC, with a phase 3 trial in China (OptiTROP-Lung07) already fully enrolled.

The approval is also great news for MSD, known as Merck & Co in the US and Canada, which licensed rights to sac-TMT in all markets outside China, Hong Kong, Macau, and Taiwan in 2022 and is now partnering with the Chinese biotech on several different ADCs.