Merck & Co.’s extensive clinical development scheme for its TROP2 antibody-drug conjugate (ADC) sac-TMT already includes 17 global phase 3 trials. But there’s one important missing piece.
The New Jersey pharma currently does not have a registrational study for the Kelun-Biotech-partnered drug in first-line PD-L1-low or -negative nonsquamous non-small cell lung cancer. Instead, the company is running a phase 3 adding sac-TMT to Keytruda in first-line maintenance squamous NSCLC regardless of PD-L1 expressions and another in PD-L1-high nonsquamous patients.
More than two years have passed since those two studies kicked off. That’s a notable hole in Merck’s whole TroFuse clinical program for what it touts as a “workhorse” product, especially as the landmark Keynote-189 trial win in first-line nonsquamous NSCLC was how Keytruda was crowned the PD-1 king.
At the American Society of Clinical Oncology annual meeting in Chicago, Kelun also showcased a positive China phase 3 trial, OptiTROP-Lung05, in PD-L1-positive NSCLC across both histologies, although the comparator of single-agent Keytruda may not apply to the U.S. in the PD-L1-low subpopulation.
Before Merck started the above two first-line NSCLC trials, it didn’t have results from the OptiTROP-Lung05 data to guide its plan, and it was not clear if sac-TMT is enough to displace chemotherapy for everyone, Marjorie Green, M.D., Merck’s head of oncology clinical development, told Fierce in an interview on the ASCO sidelines.
The U.S. pharma didn’t want to just pile the ADC on Keytruda and chemo because this approach has not been as successful in solid tumors as in blood cancers, she explained, possibly because a compromise has to be made on dosing strengths to control toxicity.
“Everyone is like, ‘When are you going to replace 189?’” Green said.
“Because of the fragmentation that’s happening in lung cancer, we didn’t want to just say, ‘Let’s throw the kitchen sink at a patient,’” she said. “Let’s try and think how practice is actually being done and design it that way.”
Fast forward to today—on top of the positive OptiTROP-Lung05 readout, Kelun is expected to report results from its phase 3 OptiTROP-Lung06 China study at the upcoming European Society of Medical Oncology annual meeting in October, the Chinese company told Fierce.
That study pits sac-TMT and Keytruda against chemotherapy and Keytruda in first-line, PD-L1-negative nonsquamous NSCLC. It would provide a direct clue to whether a global twin by Merck would be viable to potentially cover a missing piece in the TroFuse program.
During a Q&A session at ASCO 2026, OptiTROP-Lung05’s principal investigator referred to the upcoming ESMO data as from OptiTROP-Lung14, which, according to Kelun, was a mix-up with an internal trial numbering system.
Separately, Merck now has a potentially more potent immunotherapy, the PD-1xVEGF inhibitor MK-2010, which Green called a “phase 3-ready” asset. But she appeared cautious about a three-drug approach here, too, because of the risk for overlapping toxicities.
“It’s possible,” Green told Fierce. “Is there going to be more toxicity that limits the effectiveness because someone’s dropping a drug that improves survival? I think it’s an open question.”
Green was tight-lipped about whether Merck will launch a next-generation phase 3 trial involving sac-TMT or MK-2010 to replace Keytruda and traditional chemo in PD-L1-low or -negative nonsquamous NSCLC, citing a “hyper-competitive environment.”
At least one thing seems clear. Even with promising early results from MK-2010 and other PD-(L)1xVEGF competitors, Green’s comments suggest Merck will likely not pursue a broad first-line NSCLC study for a combination of MK-2010 and chemo like its competitors Summit Therapeutics, Pfizer and a BioNTech-Bristol Myers Squibb alliance are doing. Merck also appears unlikely to use this approach for sac-TMT, despite AstraZeneca and Daiichi Sankyo adopting this strategy for their TROP2 ADC Datroway in the closely watched Avanzar trial.
“I think shotgun approaches are not the best approaches in oncology,” Green said. “We got spoiled with Keytruda and other drugs because they … are working on the immune system, and that’s not tumor-specific.”
“We want to always plan our portfolio for what is care going to look like in three to five years,” she said, “not what does it look like today.”
Editor's Note: The story was updated at 3 p.m. ET, June 1, to clarify the OptiTrop-Lung14 code.