Sac-TMT Plus Pembrolizumab Nets BTD in China for First-Line PD-L1+ NSCLC

The Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) has granted breakthrough therapy designation to the TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; formerly SKB264/MK-2870) plus pembrolizumab (Keytruda) for the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC)with a PD-L1 tumor proportion score (TPS) of at least 1% as well as EGFR- and ALK-negative disease.¹

The combination is being examined for the treatment of patients with locally advanced or metastatic NSCLC in the phase 3 OptiTROP-Lung05 trial (NCT06448312). In November 2025, Sichuan Kelun-Biotech Biopharmaceutical Co, the developer of sac-TMT, announced that the study met its primary end point after the combination displayed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs pembrolizumab monotherapy.² A positive trend in favor of the investigational arm in terms of overall survival (OS) was also reported. In a news release, the company noted that this was the first phase 3 study of an ADC plus an immune checkpoint inhibitor to achieve its primary end point in frontline NSCLC.

What is the design of OptiTROP-Lung05?

OptiTROP-Lung05 is an ongoing randomized, open-label, multicenter trial that is recruiting patients with PD-L1–positive locally advanced or metastatic NSCLC.³ Eligible patients need to have stage IIIB/IIIC or stage IV disease that is not amenable to radical surgery and/or radical radiotherapy regardless of concurrent chemotherapy, a PD-L1 TPS of at least 1%, at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1 with no worsening within 7 days prior to random assignment, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function. Additionally, patients cannot have received prior systemic anticancer therapy for locally advanced or metastatic disease and must be 18 years to 75 years old.

Patients with an active second malignancy, uncontrolled or clinically significant cardiovascular disease, a history of or current noninfectious pneumonitis/interstitial lung disease, active infection requiring systemic therapy within 2 weeks of random assignment, or active hepatitis B or C viral infection are being excluded from enrollment. Additional exclusion criteria include HIV-positive or a history of acquired immunodeficiency syndrome, a known active syphilis infection, a known allergy to sac-TMT or pembrolizumab, or having undergone major surgery within 4 weeks prior to random assignment or being expected to undergo major surgery during the study.

Patients will be randomly assigned 1:1 to receive intravenous (IV) sac-TMT on days 1, 15, and 29 of each 6-week cycle in combination with IV pembrolizumab on day 1 of each 6-week cycle or pembrolizumab monotherapy. Pembrolizumab is being administered at the same dose in the active comparator arm as in the investigational arm.

The primary end point is PFS assessed by blinded independent central review. Secondary end points include OS, investigator-assessed PFS, objective response rate, disease control rate, duration of response, and time to response.

What other designations have been granted to sac-TMT in NSCLC?

In December 2024, the FDA granted breakthrough therapy designation to sac-TMT for the treatment of patients with advanced or metastatic nonsquamous NSCLC harboring EGFR mutations who experienced disease progression on or after a TKI and platinum-based chemotherapy.⁴ In March 2025, the NMPA approved sac-TMT in EGFR-mutant locally advanced or metastatic nonsquamous NSCLC following disease progression on an EGFR TKI and platinum-based chemotherapy.⁵

References

1. Kelun-Biotech announces breakthrough therapy designation granted in China for sacituzumab tirumotecan (sac-TMT) in combination with immunotherapy pembrolizumab for first-line treatment of PD-L1-positive NSCLC. News release. Sichuan Kelun-Biotech Biopharmaceutical Co. January 5, 2026. Accessed January 6, 2026. https://en.kelun-biotech.com/newsCenter.aspx?mid=18
2. Kelun-Biotech announces phase III trial of sac-TMT in combination with Keytruda (pembrolizumab) as first-line treatment for PD-L1-positive NSCLC met primary endpoint. News release. Sichuan Kelun-Biotech Biopharmaceutical Co. November 24, 2025. Accessed January 6, 2026. https://www.prnewswire.com/news-releases/kelun-biotech-announces-phase-iii-trial-of-sac-tmt-in-combination-with-keytruda-pembrolizumab-as-first-line-treatment-for-pd-l1-positive-nsclc-met-primary-endpoint-302624279.html
3. A study of SKB264 in combination with pembrolizumab versus pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated December 8, 2025. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT06448312
4. FDA grants breakthrough designation to sacituzumab tirumotecan (sac-TMT) for the treatment of certain patients with previously treated advanced or metastatic nonsquamous non-small cell lung cancer with EGFR mutations. News release. Merck. December 3, 2024. Accessed January 6, 2026. https://www.merck.com/news/fda-grants-breakthrough-therapy-designation-to-sacituzumab-tirumotecan-sac-tmt-for-the-treatment-of-certain-patients-with-previously-treated-advanced-or-metastatic-nonsquamous-non-small-cell-lung-ca/
5. Kelun-Biotech’s TROP2 ADC sacituzumab tirumotecan (sac-TMT) approved for marketing in second indication by NMPA for EGFRm NSCLC. News release. Sichuan Kelun-Biotech Biopharmaceutical Co. March 10, 2025. Accessed January 6, 2026. https://www.prnewswire.com/news-releases/kelun-biotechs-trop2-adc-sacituzumab-tirumotecan-sac-tmt-approved-for-marketing-in-second-indication-by-nmpa-for-egfrm-nsclc-302396917.html