NEJM and ESMO Publish OptiTROP-Lung06 Results: sac-TMT Plus Pembrolizumab Extends PFS

Before this readout, the standard first-line regimen for PD-L1-negative (TPS<1%) advanced nonsquamous NSCLC without EGFR or ALK alterations was pembrolizumab plus pemetrexed and platinum chemotherapy, but the accompanying NEJM paper states in its background that outcomes for these patients remain suboptimal [Peer-reviewed·L]. The trial is registered on ClinicalTrials.gov as NCT06711900, a phase 3, randomized, open-label study comparing SKB264 plus pembrolizumab versus chemotherapy plus pembrolizumab, with BICR-assessed PFS as primary endpoint; notably, the registry lists a planned enrollment of 432 with start on 2024-10-30, while the press release states 455 patients were actually enrolled, an inconsistency between the two sources . The sponsor is Sichuan Kelun-Biotech, consistent with the funding statement in the NEJM paper [Peer-reviewed·L].

The key data come from the prespecified interim analysis, with a data cutoff of June 9, 2026 and median follow-up of 9.7 months. A total of 455 patients were randomized 1:1 (229 to the combination arm, 226 to chemotherapy plus pembrolizumab) [Peer-reviewed·L]. By BICR assessment, median PFS was 15.0 months (95% CI 9.9-NE) versus 5.7 months (95% CI 5.5-7.4), a 51% reduction in risk of progression or death (HR 0.49; 95% CI 0.36-0.65; P<0.0001). OS, a secondary endpoint, showed HR 0.58 (95% CI 0.38-0.88) at interim analysis, with median OS not reached in either arm, indicating a trend toward benefit. On safety, grade ≥3 treatment-emergent adverse events were less frequent in the combination arm than in the chemotherapy control arm, as were TEAEs leading to dose reduction or permanent discontinuation; interstitial lung disease/pneumonitis rates were similar between arms, with no new safety signals. The paper concludes the combination significantly prolonged first-line PFS [Peer-reviewed·L] (needs verification).

This result moves sac-TMT, the TROP2 ADC from Kelun-Biotech's collaboration with MSD, to a new position: the company describes it as the first TROP2 ADC approved in a lung cancer indication, with 4 approved indications in China, and its new indication application for first-line use with pembrolizumab in PD-L1 TPS≥1% EGFR/ALK-negative NSCLC has been accepted by NMPA under priority review. OptiTROP-Lung06 fills in the PD-L1-negative population; lead investigator Professor Caicun Zhou noted that, combined with the OptiTROP-Lung05 results presented at ASCO 2026, the regimen shows PFS benefit across PD-L1 expression statuses in driver-gene-negative NSCLC. The registry lists primary completion expected in December 2026 , and ex-Greater China development is being advanced by MSD within its 18 ongoing global phase 3 studies (MSD-sponsored) (needs verification).

Information not yet disclosed or pending confirmation includes: ORR, deep response rate, and median duration of response were mentioned in the press release but could not be verified against primary sources such as regulatory documents or the registry (the NEJM abstract excerpt also did not fully report them), pending the full publication; OS remains immature and awaits final analysis. On the regulatory front, submission status for this PD-L1-negative indication is undisclosed; near-term domestic milestones include review progress on the two accepted new indication applications and readouts from 9 domestic registrational studies. This article does not constitute investment advice (needs verification).