Among a series of data readouts of sac-TMT (TROP2 ADC) at ESMO, we highlight two pivotal Ph3 readouts that strengthen sac-TMT’s profile across NSCLC and endometrial cancer (EC). In 1L PD-L1-negative nsq-NSCLC, OptiTROP-Lung06 showed mPFS of 15.0 vs 5.7 months (HR 0.49) with lower grade ≥3 TEAEs and discontinuations versus chemo-IO, supporting a China NDA. Together with Lung05 in PD-L1-positive disease, these results establish activity across the PD-L1 spectrum and support sac-TMT as a differentiated IO partner to combo with both PD-1 mAb and PD-1/VEGF bsAb. In 2L+ EC, global TroFuse-005 delivered improvements in mPFS (7.2 vs 3.9 months), mOS (19.0 vs 12.1 months) and ORR (35.1% vs 17.3%), providing the first global Ph3 validation for sac-TMT. With 17 global Ph3 trials ongoing, we expect MSD to accelerate global development, with MK-2010 (PD-1/VEGF bsAb) combinations and multiple Ph3 readouts as key catalysts.

OptiTROP-Lung06: Compelling Ph3 readout in 1L PD-L1–negative nsq-NSCLC. Ph3 OptiTROP-Lung06 randomized 455 patients with previously untreated advanced PD-L1–negative (TPS <1%) nsq-NSCLC without sensitizing EGFR/ALK alterations to sac-TMT plus pembrolizumab (n=229) or pemetrexed/platinum plus pembrolizumab (n=226). At 9.7 months of median follow-up, BICR-assessed mPFS was 15.0 vs 5.7 months (HR 0.49; P<0.0001), with 12-month PFS rates of 51.1% vs 22.8%. ORR was similar (50.2% vs 47.3%), but the sac-TMT combination generated deeper responses (28.8% vs 17.3%) and longer mDoR (13.6 vs 6.8 months; HR 0.47), indicating that response durability rather than initial response drove the PFS benefit. The control arm’s 5.7 months of mPFS was broadly consistent with the 6.2 months reported for PD-L1 <1% disease in KEYNOTE-189 (link). Early OS was also encouraging (HR 0.58; 95% CI 0.38–0.88), although subsequent chemotherapy use was higher in the sac-TMT arm (50.5% vs 33.3%). Grade ≥3 TEAEs (47.6% vs 60.6%) and TEAEs leading to discontinuation of any study drug (5.7% vs 14.2%) were lower in the sac-TMT arm, supporting the potential of sac-TMT to replace conventional chemotherapy without compromising efficacy. Stomatitis was more frequent with sac-TMT arm (51.1% vs 8.4%), but grade ≥3 stomatitis occurred in only 2.2% of patients; all ocular surface toxicities were grade 1–2.

OptiTROP-Lung05/06 support sac-TMT across the PD-L1 spectrum and pave the way for global Ph3 combinations with IO2.0. Kelun Biotech has recently submitted a China NDA for sac-TMT plus pembrolizumab in 1L PD-L1-negative nsq-NSCLC based on OptiTROP-Lung06. In PD-L1-positive disease, Lung05 demonstrated compelling efficacy versus pembrolizumab monotherapy, with ORR of 70.2% vs 42.0% and a PFS hazard ratio of 0.35; subgroup analyses showed PFS HRs of 0.28 and 0.47 in patients with TPS 1-49% and TPS ≥50%, respectively. The China NDA for 1L PD-L1-positive NSCLC based on Lung05 was submitted in May 2026. Taken together, the Lung05/06 datasets position sac-TMT as a potentially differentiated and preferred immuno-oncology combination partner across the full PD-L1 expression spectrum in 1L NSCLC. Meanwhile, MSD is reevaluating its global 1L NSCLC strategy, with management indicating a willingness to move beyond the traditional KEYNOTE-189-style regimen and consider sac-TMT as a potential next-generation chemotherapy backbone. In this context, MSD is assessing both pembrolizumab and its PD-1/VEGF bispecific antibody MK-2010 as combination partners. Notably, the Ph2 MK-2010-003 study, evaluating MK-2010 plus sac-TMT in advanced solid tumors, was initiated in Oct 2026. MSD also plans to initiate a Ph3 study of MK-2010 plus sac-TMT in 1L NSCLC in 1H27. In parallel, global Ph3 studies of sac-TMT combined with pembrolizumab in PD-L1 TPS ≥50% NSCLC, squamous maintenance, and adjuvant NSCLC remain ongoing.