Kelun-Biotech’s TROP2 ADC Sac-TMT Shows Durable Activity Across Genomically Altered NSCLC in a Phase 2 Study
Sichuan Kelun-Biotech has reported new Phase 2 data for its TROP2-directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) in heavily pretreated non-small cell lung cancer (NSCLC), showing durable antitumor activity across patients harboring a diverse range of actionable genomic alterations.
The results, to be presented at the upcoming 2026 World Conference on Lung Cancer (WCLC 2026), expand the clinical evidence for sac-TMT beyond NSCLC carrying the more common sensitizing EGFR mutations and suggest the ADC may have activity across molecularly heterogeneous forms of advanced lung cancer.
In the Phase 2 multicohort study NCT05631262, 90 patients with previously treated locally advanced or metastatic NSCLC carrying genomic alterations including uncommon EGFR mutations, EGFR exon 20 insertions, ALK fusions, KRAS mutations, ROS1 fusions and other alterations were evaluated.
At a median follow-up of 21.2 months, sac-TMT produced an objective response rate (ORR) of 34.4% (31 of 90 patients), while responding patients achieved a median duration of response (DOR) of 12.7 months.
The findings are notable given the heavily pretreated and molecularly diverse population and add another piece to a rapidly growing clinical dataset supporting sac-TMT in lung cancer.
A Broad Genomic Population Beyond Classic EGFR Mutations
Targeted therapies have transformed the treatment of molecularly defined NSCLC, but treatment options become increasingly limited after patients develop resistance to targeted agents and chemotherapy.
The WCLC analysis examined sac-TMT in patients whose tumors carried actionable genomic alterations beyond the classic sensitizing EGFR mutations that have historically dominated targeted NSCLC drug development.
The population included patients with EGFR G719X, S768I or L861Q mutations; EGFR exon 20 insertions (ex20ins); ALK fusions; KRAS mutations; ROS1 fusions; and other genomic alterations.
Patients had received a median of two previous lines of systemic therapy, and 68.9% had previously received platinum-based chemotherapy.
This makes the approximately one-third response rate particularly relevant because the study was evaluating sac-TMT after established targeted or systemic treatment options had already been used.
The study is registered as NCT05631262 on ClinicalTrials.gov, a Phase 2, open-label, multicohort trial sponsored by Kelun-Biotech evaluating sac-TMT monotherapy in selected patients with advanced solid tumors.
Sac-TMT Delivers 34.4% ORR With Responses Lasting More Than a Year
Among the 90 evaluable patients, investigators reported:
- ORR: 34.4% (31/90)
- Median DOR: 12.7 months
- Median follow-up: 21.2 months
The duration of response may be one of the more important aspects of the dataset.
A response rate of roughly 34% indicates substantial antitumor activity in this later-line setting, but the 12.7-month median DOR suggests that responses can also be relatively durable in patients who benefit.
The results also build on earlier data from the same Phase 2 program.
At the 2025 ASCO Annual Meeting, investigators reported preliminary results in 42 patients specifically carrying uncommon EGFR mutations. At a median follow-up of 9.2 months, sac-TMT achieved a 35.7% ORR, an 85.7% disease control rate and median progression-free survival of 9.5 months. (Journal of Clinical Oncology)
The earlier cohort included 23 patients with EGFR G719X, S768I or L861Q mutations and 19 with EGFR exon 20 insertions.
The expanded WCLC dataset therefore provides longer follow-up while broadening the molecular population beyond uncommon EGFR alterations.
Manageable but Hematologically Significant Safety Profile
The safety findings remained consistent with the known profile of sac-TMT.
Among the 90 patients, 56.7% experienced Grade 3 or higher treatment-related adverse events (TRAEs), while 18.9% experienced treatment-related serious adverse events (TRSAEs).
The most frequently reported Grade 3 or higher TRAEs were:
- Neutropenia: 42.2%
- Decreased white blood cell count: 24.4%
- Anemia: 17.8%
- Stomatitis: 7.8%
Importantly, no treatment-related adverse event resulted in treatment discontinuation or death.
Hematologic toxicity therefore remains an important consideration for sac-TMT, particularly neutropenia, but the absence of treatment-related discontinuations or deaths in this analysis supports the feasibility of managing those adverse events.
The results are also broadly consistent with earlier data. In the 42-patient uncommon-EGFR analysis presented at ASCO 2025, Grade 3 or higher TRAEs occurred in 52.4% of patients, with neutropenia again the most common severe treatment-related toxicity. (Journal of Clinical Oncology)
What Is Sacituzumab Tirumotecan?
Sac-TMT, also known as SKB264 and MK-2870, is a next-generation TROP2-directed ADC originally developed by Kelun-Biotech using its proprietary OptiDC platform.
The ADC combines a TROP2-targeting antibody with a belotecan-derived topoisomerase I inhibitor payload, connected through a hydrolytically cleavable linker. (Journal of Clinical Oncology)
TROP2 is highly expressed across numerous epithelial cancers, making it an attractive target for delivering potent cytotoxic payloads directly to malignant cells.
Kelun-Biotech lists sac-TMT among the leading programs in its oncology ADC portfolio, with development spanning lung cancer, breast cancer and other solid tumors.
The drug is also known internationally as MK-2870 through Kelun-Biotech’s collaboration with Merck & Co. (MSD outside the United States and Canada), which is pursuing a broad global development program for the ADC.
Sac-TMT Is Already Approved in China
Sac-TMT is no longer simply an investigational ADC in China.
Under the Chinese brand name 佳泰莱®, the drug has accumulated multiple approvals. According to Kelun-Biotech, the NMPA has approved sac-TMT across four indications, including triple-negative breast cancer (TNBC), EGFR-mutated NSCLC and HR-positive/HER2-negative breast cancer. (Kelun-Biotech)
Its development in EGFR-mutated lung cancer has been supported by increasingly mature randomized evidence.
In a randomized study published in The BMJ, sac-TMT was compared with docetaxel in previously treated EGFR-mutated advanced NSCLC. Independent review found an ORR of 45% with sac-TMT versus 16% with docetaxel, while median PFS was 6.9 months versus 2.8 months, respectively. (PubMed)
The study also showed a survival signal: the 12-month overall survival rate was 73% with sac-TMT versus 54% with docetaxel.
Those results established that sac-TMT’s activity in EGFR-mutated NSCLC could translate into clinically meaningful benefit compared with conventional chemotherapy.
WCLC Data Broaden the Sac-TMT NSCLC Story
The new WCLC dataset addresses a somewhat different question: Can sac-TMT work across NSCLC driven by a wider range of oncogenic alterations after targeted therapies and other standard treatments have been exhausted?
The 34.4% response rate suggests that it can produce clinically meaningful responses across a heterogeneous molecular population.
That matters because ADCs are increasingly being developed as treatments that can potentially operate downstream of genomic resistance.
Unlike kinase inhibitors, which generally depend on continued dependence on a specific oncogenic signaling pathway, TROP2 ADCs exploit surface antigen expression to deliver cytotoxic payloads into tumor cells. In principle, this may allow an ADC such as sac-TMT to remain active after resistance mechanisms undermine earlier targeted therapies.
The WCLC results support that hypothesis, although randomized studies will ultimately be required to determine how sac-TMT compares with alternative later-line treatments within individual genomic subgroups.
OptiTROP-Lung04 Adds Another Dimension
Kelun-Biotech also presented an analysis from OptiTROP-Lung04 at WCLC 2026 examining sac-TMT in patients with EGFR-mutated NSCLC according to metastatic burden.
The presentation, PT2.01.04, “Sacituzumab Tirumotecan in EGFR-Mutated NSCLC Patients With ≤3 Metastatic Sites: Subgroup Analysis of OptiTROP-Lung04,” explores whether patients with relatively limited metastatic disease derive particular benefit from sac-TMT.
Together, the OptiTROP-Lung04 subgroup work and the NCT05631262 multicohort analysis illustrate how Kelun-Biotech is increasingly dissecting the NSCLC population beyond a simple EGFR-positive versus EGFR-negative framework.
Sac-TMT Emerging as a Major TROP2 ADC Competitor
The WCLC results further strengthen sac-TMT’s position within the increasingly competitive TROP2 ADC field.
The drug now has clinical evidence spanning several molecularly distinct forms of NSCLC, while Kelun-Biotech and its partners are also exploring combinations with immunotherapy.
In January 2026, China’s CDE granted Breakthrough Therapy Designation to sac-TMT plus pembrolizumab for first-line treatment of locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% and without EGFR or ALK alterations. (Kelun-Biotech)
This means the program is increasingly moving across the NSCLC treatment continuum—from later-line molecularly driven disease toward earlier-line treatment and immunotherapy combinations.
A Potential Post-Targeted-Therapy Option Across Molecular Subtypes
The latest WCLC data offer an important signal that sac-TMT’s activity may not be confined to the common EGFR-mutated population where the ADC has already generated strong clinical evidence.
In 90 heavily pretreated patients carrying a variety of genomic alterations, sac-TMT generated responses in roughly one in three patients, with those responses lasting a median of more than a year.
The toxicity profile remains characterized primarily by hematologic adverse events—particularly neutropenia—but no treatment-related discontinuations or deaths were reported in the analysis.
For Kelun-Biotech and its global development partner, the larger strategic implication is significant: TROP2-directed ADC therapy could potentially become a broadly applicable treatment after resistance to genotype-specific therapies, rather than requiring a separate ADC strategy for every oncogenic driver.
The next questions will be whether the activity seen at WCLC holds up within individual molecular subgroups—including ALK, KRAS, ROS1, EGFR exon 20 insertion and uncommon EGFR disease—and whether randomized trials can translate these response and durability signals into improvements in progression-free and overall survival.
References
- ClinicalTrials.gov — NCT05631262: SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors.
ClinicalTrials.gov study record - Journal of Clinical Oncology — Sacituzumab tirumotecan in previously treated advanced NSCLC harboring uncommon EGFR mutations. ASCO 2025 Abstract 8615.
JCO abstract - Fang W, et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced NSCLC. The BMJ, 2025.
PubMed record - Kelun-Biotech — Sacituzumab Tirumotecan (sac-TMT/SKB264/MK-2870) Pipeline.
Kelun-Biotech product pipeline - Kelun-Biotech — Sacituzumab Tirumotecan Product Information and Approved Indications in China.
Sac-TMT product page - Kelun-Biotech — Breakthrough Therapy Designation for sac-TMT plus pembrolizumab in first-line PD-L1-positive NSCLC, January 2026.
Kelun-Biotech newsroom - World Conference on Lung Cancer 2026 — New sac-TMT analyses in genomically altered NSCLC and OptiTROP-Lung04.
WCLC 2026 presentation: PT2.01.04 — Sacituzumab Tirumotecan in EGFR-Mutated NSCLC Patients With ≤3 Metastatic Sites: Subgroup Analysis of OptiTROP-Lung04.
