The clinical blueprint for Merck & Co.’s prized TROP2-directed antibody-drug conjugate, sacituzumab tirumotecan (sac-TMT), could add a missing piece thanks to a landmark achieved by its partner Kelun-Biotech.
Kelun has announced that its phase 3 OptiTROP-Lung06 study successfully met its primary endpoint. 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 (NSCLC).
At an interim analysis, the ADC/PD-1 combo demonstrated a statically significant and clinically meaningful improvement in progression-free survival compared with Keytruda combined with traditional pemetrexed and platinum-based chemo, Kelun said. A positive trend in overall survival was also observed.
The readout marks an important landmark, representing the world’s first phase 3 trial of an ADC combined with an immune checkpoint inhibitor to hit its primary endpoint in first-line, PD-L1-negative nonsquamous NSCLC.
Leerink Partners analysts led by Daina Graybosch, Ph.D., see a more profound implication. The OptiTROP-Lung06 win “delivers the first, direct proof-of-concept for an ADC replacing platinum-based chemo in a 1L NSCLC standard-of-care (SoC) regimen,” the team wrote in a July 15 note.
Previously, sac-TMT already reported strong Keytruda combination data versus Keytruda alone in the phase 3 OptiTROP-Lung05 trial for PD-L1-positive NSCLC. Critics have pointed out that Keytruda monotherapy is only a standard of care for a subgroup of patients with PD-L1-high tumors, whereas Keytruda plus chemo is the go-to regimen for PD-L1-low patients. Still, the drug’s performance in the PD-L1-low subgroup also appeared robust compared to Keytruda plus chemo by cross-trial comparison.
Now, the OptiTROP-Lung06 readout in a PD-L1-negative setting supports that sac-TMT plus Keytruda “may beat SoC in NSCLC, regardless of PD-L1 expression,” with the caveat that it’s a China-only study, Jefferies analysts wrote in a July 15 note.
It also directly addresses a jarring gap in Merck’s massive, 17-trial global phase 3 development program for sac-TMT. In first-line NSCLC, the New Jersey pharma currently has a registrational study for the ADC as a maintenance treatment for squamous cancer and another in PD-L1-high nonsquamous patients.
This gap was notable because nonsquamous NSCLC represents the core legacy of Keytruda’s dominance—it was the landmark Keynote-189 trial, which established Keytruda plus chemo as the standard in first-line nonsquamous NSCLC, that crowned Keytruda the PD-1 king.
The latest Kelun trial outcome “should give Merck confidence to run a similar global study to replace the Keynote-189 SoC in PD-L1 negative patients,” who represent a third of the first-line nonsquamous population, Leerink’s analysts argued.
As to whether Merck could also target replacing platinum chemo with sac-TMT in PD-L1-low patients, Leerink analysts suggested that it will likely depend on the strength of the OptiTROP-Lung06 data. Following the OptiTROP-Lung05 results at the 2026 American Society of Clinical Oncology annual meeting, Kelun told Fierce that the -Lung06 data are planned for the upcoming European Society of Medical Oncology annual meeting in October.
When asked about Merck’s plan to fill that gap in sac-TMT’s phase 3 program, Marjorie Green, M.D., Merck’s head of oncology clinical development, noted to Fierce Pharma that the lung cancer market has become fragmented, suggesting that a blanket study replicating Keynote-189 will not likely be the company’s strategy.
She also noted that Merck was wary of simply “throwing the kitchen sink” at patients by piling on multiple drugs, including combining ADC with PD-1 and chemo, citing risks for overlapping toxicities.
AstraZeneca and partner Daiichi Sankyo are pursuing that strategy with the closely watched Avanzar trial, which is expected to read out this year. The phase 3 study is combining the pair’s rival TROP2 ADC, Datroway, with AZ’s PD-L1 inhibitor Imfinzi and chemo in first-line NSCLC, with its primary endpoints focused on nonsquamous patients. That study could also guide Merck’s plan for sac-TMT.
During that interview on the sidelines of the ASCO 2026 meeting, Green would not divulge Merck’s plan for sac-TMT in PD-L1-low or -negative nonsquamous NSCLC, citing a “hyper-competitive environment.”
“But I do think that it is important for us to look at our portfolio and look at our OptiTROP data and think about—it’s very consistent across every subgroup. It’s consistent across histologies and there’s still opportunity there. And we have lots of things we can combine with in our portfolio,” Green said during a Merck investor event at ASCO.
In a July 15 statement to Fierce, a Merck spokesperson said the OptiTROP-Lung06 results “increase our confidence in the potential of sac-TMT to improve treatment options in the first line for patients with non-small cell lung cancer.”
In a potential alternative to a sac-TMT/Keytruda combo, Jefferies noted that Merck could move forward with pairing sac-TMT with its PD-1xVEGF bispecific, MK-2010.