Kelun has announced that its phase 3 OptiTROP-Lung06 study successfully met its primary endpoint in a significant win for its antibody-drug conjugate pipeline.
The Chinese trial evaluated sac-TMT in combination with Merck’s Keytruda as a first-line treatment for PD-L1-negative nonsquamous non-small cell lung cancer, known as NSCLC.
In an interim analysis, the ADC and PD-1 combination demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus standard treatment options.
The comparison was made against Keytruda combined with traditional pemetrexed and platinum-based chemotherapy, with a positive trend in overall survival also observed.
The readout marks an important global landmark, representing the world’s first phase 3 trial of an ADC combined with an immune checkpoint inhibitor to hit its primary endpoint in this specific patient population.
Analysts at Leerink Partners, led by Daina Graybosch, Ph.D., see a more profound implication in the result, noting it directly addresses a gap in Merck’s broader development program.
Merck currently holds exclusive rights to develop and commercialize sac-TMT outside Greater China and has 17 ongoing global phase 3 studies evaluating the molecule.
In first-line NSCLC, Merck has a registrational study for the ADC as a maintenance treatment for squamous cancer and another targeting PD-L1-high nonsquamous patients, leaving PD-L1-negative nonsquamous disease unaddressed.
This gap is particularly notable because nonsquamous NSCLC represents the core legacy of Keytruda’s dominance, established through the landmark Keynote-189 trial that made Keytruda the standard in first-line nonsquamous NSCLC.
The trial “delivers the first, direct proof-of-concept for an ADC replacing platinum-based chemo in a 1L NSCLC standard-of-care regimen,” Leerink Partners wrote in a note to investors.
Professor Caicun Zhou, National Lead Principal Investigator from Shanghai East Hospital, Tongji University, said: “For patients with driver gene-negative and PD-L1-negative NSCLC, immunotherapy combined with chemotherapy remains the current standard first-line treatment and has improved patient outcomes to some extent.”
Professor Zhou added: “However, long-term survival benefit remains limited,” underlining the clinical need that sac-TMT is now positioned to address in this difficult-to-treat population.
The phase 3 win “builds on the ADC’s strong clinical momentum,” Leerink Partners analysts noted, pointing to a phase 3 endometrial cancer trial in which sac-TMT hit its primary endpoints in May.
The positive results follow an earlier phase 3 win in the OptiTROP-Lung05 study for first-line PD-L1-positive NSCLC, strengthening the clinical evidence base for sac-TMT across a broader range of first-line NSCLC patients.
The readout could now inspire Merck to fill the remaining gap in its global phase 3 program, according to analysts, potentially broadening the commercial opportunity for sac-TMT across the full NSCLC spectrum.