Merck & Co. has said many new products will be needed to absorb the coming financial impact when its blockbuster cancer medicine Keytruda loses patent protection. One, discovered by China-based Kelun-Biotech and licensed to Merck a few years ago, has now come to the forefront.
Dubbed sacituzumab tirumotecan, or sac-TMT, the therapy is part of a class of “antibody-drug conjugates” drugmakers see as potentially supplanting traditional chemotherapy in many cancers. Merck has been so encouraged by the clinical results it’s seen so far that it’s put the drug into a sprawling Phase 3 program consisting of 17 studies in a range of tumor types.
Sac-TMT “could be one of our cornerstone ADCs, and that's why you see our conviction in all of these trials,” said Shweta Jain, who oversees Merck’s oncology assets, in an interview with BioPharma Dive.
Fresh data being presented at the American Society of Clinical Oncology conference have placed the drug firmly on investors’ radars. Abstracted study results ahead of the meeting showed that, after a median of 10.5 months of follow-up, a combination of sac-TMT and Keytruda cut the risk of disease progression or death by 65% compared to Keytruda alone in a Phase 3 trial in lung cancer in China. A “favorable trend” on survival has been observed, too, though it’s too early to tell the magnitude of the treatment’s benefit.
Safety was also seen by some analysts as cleaner than expected. Merck shares have climbed over 5% since, thanks to optimism about the therapy’s outlook.
Detailed data presented at the meeting Friday paint a more complete picture. The benefits reported were seen “across major subgroups,” including those with “squamous” and “non-squamous” disease or those with wide-ranging levels of a protein, PD-L1, associated with drug responses, according to the presentation.
Median progression-free survival hasn’t been reached among sac TMT recipients overall or within the subgroups tied to PD-L1 levels. By comparison, those in the Keytruda-only group saw their tumors advance after a median of 5.7 months.
The data are "giving us an increasing level of confidence as we get into our global studies," Jain said.
Still, there are uncertainties about sac-TMT’s potential. The drug is one of several ADCs targeting the protein TROP2. Another, AstraZeneca and Daiichi Sankyo’s Datroway, obtained narrower-than-expected use in second-line lung cancer after disappointing study results, though it’s now in late-stage testing in newly diagnosed patients. A third, Gilead Sciences’ Trodelvy, is in a Phase 3 trial in frontline lung cancer.
In a Wednesday note, Leerink Partners analyst Daina Graybosch wrote how experts she’d spoken to were unsure if the sac-TMT findings would carry over to global trials. Kelun’s study didn’t use a Keytruda-chemotherapy combination — the main treatment for non-small cell lung cancer — as a control, rendering key comparisons difficult to make.
The size of the survival benefit will be crucial in assessing sac-TMT’s potential as well, she added.
These drugs’ development also coincides with a push to prove a different kind of medicine, “PD-1/VEGF inhibitors,” could become a new treatment standard in lung cancers and other tumors. Their progress could make it harder for sac-TMT to stand out.
Jain, for her part, points to technical differences, such as the chemical “linker” in sac-TMT, to support Merck’s belief that it’ll deliver better outcomes than other TROP2-targeting drugs. She noted how it’s still unclear where PD-1/VEGF drugs — of which Merck has one — still work best. She also expressed faith the “consistent benefits” seen in testing of sac-TMT so far would hold up as the international studies begin producing results. One, in endometrial cancer, has already succeeded.
“We think that the future is bright,” she said.
