The competition among three TROP2 antibody-drug conjugates is entering a new stage as Kelun-Biotech’s Merck & Co.-partnered sacituzumab tirumotecan (sac-TMT) has become the second therapy in the class to win a marketing approval.
Chinese regulators have approved sac-TMT to treat patients with advanced triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies, including at least one in the advanced setting, Kelun said Wednesday.
Sac-TMT’s nod matches the first-in-class blessing that Gilead Sciences’ Trodelvy secured from China’s National Medical Products Administration in June 2022. Trodelvy has not been placed on China’s national reimbursement drug list since then. Chinese authorities are scheduled to release the new roster Thursday following a round of price negotiations in October.
Sac-TMT, also known as SKB264 or MK-2870, represents the first asset in Kelun’s multitarget, multibillion-dollar ADC collaboration with Merck. In May 2022, the New Jersey pharma obtained ex-China rights to the drug by paying $47 million upfront and committing up to $1.36 billion in potential milestones.
The approval is based on results from the phase 3 OptiTROP-Breast01 trial conducted in China. Among TNBC patients who have received at least two prior therapies, sac-TMT significantly reduced the risk of death by 47% compared with a physician’s choice of chemotherapy. At an interim analysis performed at a median follow-up of 10.4 months, patients in the chemo arm lived a median 9.4 months, while the median overall survival was not reached with sac-TMT.
Sac-TMT also significantly reduced the risk of progression or death by 69% versus chemo. The median progression-free survival time was 5.7 months versus 2.3 months, respectively.
Merck and Kelun are trying to bring sac-TMT to earlier TNBC treatment settings. The Merck-sponsored TroFuse-12 trial is testing sac-TMT in combination with Merck’s Keytruda as a postsurgical adjuvant therapy in patients who didn’t achieve a pathological complete response after neoadjuvant therapy.
In addition, a Kelun-initiated China-only phase 3 trial coded SKB264-III-11 is evaluating sac-TMT as a first-line therapy. Meanwhile, rival Gilead has ASCENT-03, a counterpart study with a similar first-line design but global in scope, expected to read out this year.
Besides TNBC, Kelun has two other sac-TMT applications under review in China: EGFR-mutated non-small cell lung cancer (NSCLC) following failure on either an EGFR inhibitor alone or both EGFR inhibitor and chemotherapy,
Previously treated EGFR-mutated NSCLC is also the indication that AstraZeneca and Daiichi Sankyo are targeting in a refiled FDA application for their TROP2 ADC contender, datopotamab deruxtecan (Dato-DXd).
AZ and Daiichi recently withdrew their original filing for Dato-DXd as a treatment for nonsquamous NSCLC after discussion with the FDA, as the phase 3 TROPION-Lung01 trial behind that submission has shown some mixed results.
Although the global study met one of its dual primary endpoints of progression-free survival, it failed to show a survival benefit for Dato-DXd. And the tumor progression advantage was limited to nonsquamous patients but not those with squamous disease. The conflicting findings prompted AZ to explore a novel biomarker for Dato-DXd, potentially reducing the size of the patient population it could target.
The market value of the TROP2 ADC class has been called into question lately. Besides Dato-DXd’s setback, Gilead’s bid to expand Trodelvy into second-line NSCLC sputtered with the failure of EVOKE-01. And the California biotech is withdrawing Trodelvy’s accelerated approval in previously treated bladder cancer following a negative readout from the TROPiCS-04 trial.
Merck, for its part, has an extensive development program for sac-TMT in NSCLC. But as TROP2 ADCs’ prospects in NSCLC look increasingly shaky, Merck, under pressure to find the next Keytruda to maintain its leadership in NSCLC, a few days ago inked a $588 million-upfront deal to in-license LaNova Medicines’ PD-1xVEGF bispecific antibody, LM-299.