Kelun-Biotech announced on July 14, 2026, that the Phase III OptiTROP-Lung06 study evaluating sacituzumab tirumotecan (sac-TMT) in combination with pembrolizumab as first-line treatment for PD-L1–negative (TPS <1%) locally advanced or metastatic non-squamous NSCLC has met its primary endpoint of progression-free survival (PFS) at a prespecified interim analysis — marking a world-first achievement for an ADC plus immune checkpoint inhibitor combination in this particularly difficult-to-treat population.

Clinical Takeaway

In a randomized head-to-head Phase III trial, sac-TMT plus pembrolizumab demonstrated statistically significant and clinically meaningful improvement in PFS compared with the current standard of care — pembrolizumab plus pemetrexed and platinum-based chemotherapy — in patients with driver gene–negative, PD-L1–negative non-squamous NSCLC. A positive trend in overall survival (OS) was also observed. This is the first Phase III trial of any ADC–immune checkpoint inhibitor combination to meet its primary endpoint in this first-line setting.

Drug Profile & Mechanism

  • Sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870; 佳泰莱®): A TROP2-directed antibody-drug conjugate (ADC) developed by Sichuan Kelun-Biotech that delivers precise cytotoxic payload to TROP2-expressing tumor cells.
  • Pembrolizumab (KEYTRUDA®): An anti-PD-1 monoclonal antibody developed by MSD that restores antitumor immune responses by blocking the PD-1/PD-L1 axis.
  • Synergistic rationale: The combination leverages sac-TMT’s ability to directly kill TROP2-expressing tumor cells while simultaneously modulating the tumor immune microenvironment, potentially unlocking PD-1 inhibitor activity in patients with absent or low PD-L1 expression who historically derive limited benefit from immunotherapy alone.

Target Population

  • Diagnosis: Locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
  • Biomarker status: Driver gene–negative (no actionable oncogenic driver mutations) and PD-L1 TPS <1% (PD-L1–negative)
  • Treatment setting: First-line (treatment-naïve) locally advanced or metastatic disease
  • Unmet need: Despite improvements with immunotherapy–chemotherapy combinations, patients with PD-L1–negative NSCLC continue to have limited long-term survival benefit from current standard-of-care regimens.

Study Design

  • Study name: OptiTROP-Lung06
  • Phase: Phase III, registrational
  • Design: Randomized, open-label, multicenter
  • Experimental arm: Sac-TMT + pembrolizumab
  • Control arm: Pembrolizumab + pemetrexed + platinum-based chemotherapy (current first-line standard of care)
  • Oversight: An Independent Data Monitoring Committee (IDMC) reviewed data at a prespecified interim analysis and confirmed the primary endpoint had been met.

Endpoints

Efficacy Outcomes

  • PFS (primary endpoint — MET): Sac-TMT plus pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in PFS versus pembrolizumab plus pemetrexed and platinum chemotherapy at the prespecified interim analysis.
  • OS (secondary endpoint): A positive trend in overall survival was observed in favor of the sac-TMT combination arm; OS data continue to mature.
  • Context within the sac-TMT program: This success follows the earlier positive readout of OptiTROP-Lung05, in which sac-TMT plus pembrolizumab demonstrated superiority over pembrolizumab monotherapy in PD-L1–positive NSCLC. Together, these two Phase III studies provide clinical evidence supporting the sac-TMT plus pembrolizumab combination across the full spectrum of PD-L1 expression in driver gene–negative non-squamous NSCLC.

Safety

  • The safety profile of sac-TMT plus pembrolizumab in OptiTROP-Lung06 was consistent with previously reported studies of this combination.
  • No new safety signals were identified at the interim analysis.
  • Full safety data will be reported at a future scientific conference and/or in peer-reviewed publication.

Regulatory Implications

  • Kelun-Biotech plans to communicate with China’s Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) regarding the OptiTROP-Lung06 results and potential regulatory pathways.
  • The companion OptiTROP-Lung05 study (PD-L1–positive NSCLC) has already supported submission of a new indication application to the CDE; results were presented as an oral report at the 2026 ASCO Annual Meeting and simultaneously published in The Lancet.
  • Sac-TMT is currently being evaluated in ten registrational studies in lung cancer, underscoring the breadth of the development program.

Key Clinical Implications

✔ First-ever Phase III win for ADC + ICI in PD-L1–negative first-line NSCLC: OptiTROP-Lung06 is the world’s first Phase III trial of an ADC combined with an immune checkpoint inhibitor to meet its primary endpoint in driver gene–negative, PD-L1–negative non-squamous NSCLC — a milestone with significant implications for how this population is treated.

✔ Chemotherapy-free backbone may replace standard pemetrexed/platinum: The trial directly challenges the current immunotherapy–chemotherapy standard of care, suggesting that replacing cytotoxic chemotherapy with a TROP2 ADC may yield superior PFS outcomes in PD-L1–negative patients.

✔ Sac-TMT + pembrolizumab now demonstrates benefit across PD-L1 expression spectrum: With positive Phase III results in both PD-L1–positive (OptiTROP-Lung05) and PD-L1–negative (OptiTROP-Lung06) populations, this combination has the potential to become a pan–PD-L1 first-line regimen for driver gene–negative non-squamous NSCLC.

✔ Mechanistic synergy addresses an immunotherapy bottleneck: The addition of a TROP2 ADC may prime the tumor immune microenvironment, potentially sensitizing PD-L1–negative tumors — which historically respond poorly to checkpoint inhibition — to PD-1 blockade.

✔ No new safety concerns identified: The safety profile remained consistent with prior studies, supporting the tolerability of this chemotherapy-free combination in a broad first-line population.

Bottom Line

The positive Phase III OptiTROP-Lung06 readout positions sac-TMT plus pembrolizumab as a potential paradigm-shifting first-line option for patients with driver gene–negative, PD-L1–negative non-squamous NSCLC — a population where current immunotherapy–chemotherapy regimens provide incomplete long-term disease control. Combined with the earlier OptiTROP-Lung05 success in PD-L1–positive disease, these data collectively support sac-TMT plus pembrolizumab as a broadly applicable chemotherapy-free strategy across PD-L1 expression levels. Regulatory discussions with China’s NMPA CDE are anticipated, and full data are expected to be presented at an upcoming scientific congress.

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