The Phase 3 results are the first direct proof-of-concept for an ADC replacing platinum-based chemo in a first-line standard-of-care regimen for non-small cell lung cancer, according to Leerink Partners. The readout also represents the second late-stage win for the Merck and Kelun-Biotech asset, called sac-TMT.
Kelun-Biotech’s Merck-partnered antibody-drug candidate sacituzumab tirumotecan, or sac-TMT, succeeded in a late-stage non-small cell lung cancer trial when combined with Merck’s oncology juggernaut Keytruda, the China-based biotech announced Tuesday.
The Phase 3 win “builds on the ADC’s strong clinical momentum,” analysts at Leerink Partners wrote in a Wednesday note to investors. In May, sac-TMT hit the primary endpoints in a Phase 3 endometrial cancer trial. This time around, the results provide the first direct proof-of-concept for an ADC replacing platinum-based chemo in a first-line NSCLC standard-of-care regimen, Leerink continued, noting the drug’s “workhorse potential.”
Sac-TMT at a pre-specified analysis met the trial’s primary endpoint, meaningfully improving progression-free survival (PFS) alongside Keytruda and chemotherapy, according to Kelun’s press release. It also showed a positive trend in overall survival (OS) compared to a Keytruda/chemotherapy combo. Kelun plans to discuss the results with China’s chief drug regulator.
According to Kelun, sac-TMT addresses the difficult PD-L1-negative non-squamous NSCLC population that doesn’t typically respond to therapies like Keytruda, which is a checkpoint inhibitor blocking the PD-1 pathway.
“The introduction of a TROP2 ADC to a PD-1 [monoclonal antibody] not only delivers ADC’s precise targeting and killing of tumor cells, but also activates the immune microenvironment through their synergetic mechanisms,” the biotech said in the release. “This strategy is expected to unlock the therapeutic potential of the PD-1 mAb in patients with PD-L1-negative or limited immune responses, breaking this therapeutic bottleneck.”
RBC analysts on Wednesday called the trial success “another positive for Merck’s sac-TMT franchise, as it extends the validated sac-TMT + Keytruda combination from the PD-L1-positive population . . . into the more challenging PD-L1-negative segment,” where immuno-oncology agents plus chemo remains the western standard of care.
Merck tied up with Kelun in December 2022 through a $1.4 billion licensing agreement comprising seven ADC candidates for cancer. The alliance was part of the company’s efforts to “augment” its oncology pipeline, according to a statement by Dean Li, president of Merck Research Laboratories, at the time.
“Advances in ADC technologies are yielding a new generation of candidates designed to more precisely target and deliver potent anticancer agents to the tumor site,” Li said.
Tuesday’s results follow sac-TMT’s May victory, when the ADC demonstrated significantly better OS and PFS compared to physician’s choice of intervention in certain patients with advanced or recurrent disease.
Looking forward, RBC analysts are tracking key milestones including data to be released at the national meeting of the European Society for Medical Oncology in October, as well as a “cleaner ex-China regulatory read-through investors require” from a global phase 3 trial expected in 2028.
