An interview with Li Zhang MD, Medical Oncologist and Full Professor, Sun Yat-sen University Cancer Center, Guangzhou, China

BERLIN, Germany—A doubling of progression-free survival, and highly statistically significant benefit for overall survival, has been achieved in patients with epidermal growth factor- (EGFR-) mutated non-small cell lung cancers that had become refractory to EGFR tyrosine kinase inhibitor therapy in a study in which treatment with the antibody drug conjugate (ADC) sacituzumab tirumotecan was compared with standard platinum-based chemotherapy.

At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Professor Li Zhang MD, a medical oncologist and full professor at Sun Yat-sen University Cancer Center in Guangzhou, China, reported findings from the randomized, multi-center phase III OptiTROP-Lung04 study at a late-breaking session.  After his talk he discussed the findings with Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCLOGY: Li Zhang MD

IN: “[GOODWIN] I’m here at ……OUT:  …..I’m Peter Goodwin  8:42 secs

ESMO ABSTRACT LBA5:

Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study

Speaker:

Li Zhang (Guangzhou, China)

Authors:

Li Zhang (Guangzhou, China) Wen Feng Fang (Guangzhou, China) Lin Wu (Changsha, China) Xiangjiao Meng (Jinan, China) Yu Yao (Xi’an, Shaanxi Province, China) Wei Zuo (Nanchang, China) Wenxiu Yao (Chengdu, China) Yanyan Xie (Nanning, China) Yu Zhang (Mianyang, China) Jiuwei Cui (Changchun, China) Yongchang Zhang (Changsha, China) Xingya Li (Zhengzhou, China) Wu Zhuang (Fuzhou, China) Jian Fang (Beijing, China) Qiming Wang (Zhengzhou, China) Wei Jiang (Nanning, China) Kai Li (Tianjin, China) Yina Diao (Chengdu, China) Junyou Ge (CHENGDU, China) Yunpeng Yang (Guangzhou, China)

Background

Sac-TMT is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. Sac-TMT demonstrated significant survival benefits over docetaxel in EGFRm NSCLC after failure of EGFR-TKI and platinum-based chemotherapy (Fang et al., BMJ 2025). Here, we first report the final PFS analysis and preplanned interim OS analysis results from the phase 3 OptiTROP-Lung04 study (NCT05870319).

Methods

Patients (pts) were randomized (1:1) to receive sac-TMT monotherapy (5 mg/kg Q2W) or chemotherapy (pemetrexed 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W for 4 cycles followed by maintenance of pemetrexed). The primary endpoint was PFS assessed by blinded independent review committee (BIRC) with OS as a key secondary endpoint tested hierarchically.

Results

A total of 376 pts (median age 59.5 yrs; 39.6% male; 79.3% ECOG PS 1; 94.7% prior 3rd-generation EGFR TKI) were randomized to the sac-TMT (n=188) or chemotherapy (n=188) groups. At a median follow-up of 18.9 mo, 21.3% of pts (sac-TMT) vs 1.6% (chemotherapy) remained on treatment. Sac-TMT demonstrated highly statistically significant and clinically meaningful improvements in PFS and OS compared to chemotherapy (Table). Grade ≥ 3 TRAEs occurred in 49.5% and 52.2%, and TRSAEs in 7.4% and 17.0% of pts in sac-TMT and chemotherapy arms, respectively. No drug-related interstitial lung disease/pneumonitis occurred in either arm.

Sac-TMT (n=188)      Chemotherapy (n=188)

Median PFS (BIRC), mo (95% CI)  8.3 (6.7 – 9.9)  4.3 (4.2 – 5.5)

HR (95% CI)  0.49 (0.39 – 0.62)

P-value          <0.0001

12-mo PFS rate, %, (95% CI)           32.3 (25.5 – 39.2)        7.9 (4.4 – 12.8)

Median OS, mo (95% CI)    NR (21.5 – NE)          17.4 (15.7 – 20.4)

HR (95% CI)  0.60 (0.44 – 0.82)

P-value          0.0006

Adjusted median OS*, mo (95% CI)          NR (21.5 – NE)          17.2 (15.4 – 18.9)

HR (95% CI)  0.56 (0.41 – 0.77)

P-value          0.0002

ORR (BIRC), % (95% CI)     60.6 (53.3, 67.7)         43.1 (35.9, 50.5)

Median DOR (BIRC), mo (95% CI)            8.3 (6.2 – 10.0)            4.2 (3.0 – 4.4)

Data cutoff: Jul 06, 2025. P-value was presented as one-sided. *censored at the date of initiation of subsequent anti-tumor ADC drug therapy.

Conclusions

Sac-TMT is the first TROP2 ADC to significantly improve PFS and OS over platinum-based chemotherapy, with manageable safety in EGFR-TKI resistant NSCLC, positioning it as a potential new standard of care for this population.

Clinical trial identification

NCT05870319.

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.