In brief
- An exploratory biomarker analysis of the phase III EVOKE-01 study tested whether Trop-2 expression or circulating tumour DNA identifies patients with NSCLC who benefit from sacituzumab govitecan rather than docetaxel.
- Trop-2 histological score did not separate the two treatments: median overall survival was 8.9 versus 9.8 months at or above the median score and 11.8 versus 10.7 months below it.
- KRAS driver alterations and TP53, KEAP1 and STK11 mutations were negative prognostic factors; patients with TP53 mutations derived more benefit from sacituzumab govitecan than from docetaxel.
Background
Sacituzumab govitecan is an antibody-drug conjugate directed at Trop-2, the trophoblast cell surface antigen. A target that can be stained in tissue invites the assumption that more of it predicts more benefit. EVOKE-01 was the open-label phase III study of sacituzumab govitecan versus docetaxel in NSCLC, and this analysis asked whether Trop-2 expression or circulating tumour DNA (ctDNA) picks out the patients it helps.
Study design
Trop-2 membrane protein expression was measured by immunohistochemistry in the Trop-2 biomarker evaluable population. Separately, ctDNA analyses assessed the baseline level and its reduction with treatment, and identified oncogenic driver alterations in KRAS, TP53, KEAP1 and STK11 along with other relevant mutations in the ctDNA biomarker evaluable population.
Trop-2 expression
Median overall survival with sacituzumab govitecan versus docetaxel was 8.9 versus 9.8 months (hazard ratio 0.96, 95% CI 0.68 to 1.38) in the subgroup with a Trop-2 histological score at or above the median, and 11.8 versus 10.7 months (hazard ratio 0.89, 95% CI 0.60 to 1.32) in the subgroup below the median. Neither subgroup showed a separation between the treatments, and the direction of the point estimates does not follow the amount of target present.
Circulating tumour DNA
Median overall survival was longest in patients with undetectable ctDNA at baseline, which the authors described as an expected result. A reduction in ctDNA was observed after the first cycle with either treatment, and the authors reported that this supports sacituzumab govitecan as an active therapy in NSCLC.
Among the mutations examined, KRAS driver alterations and the potential immunotherapy resistance mutations TP53, KEAP1 and STK11 were negative prognostic factors in this second-line population. Patients with TP53 mutations derived more benefit from sacituzumab govitecan than from docetaxel. Sacituzumab govitecan activity was observed independent of DNA damage repair mutations.
What comes next
The authors concluded that Trop-2 expression did not identify patients benefiting more from sacituzumab govitecan than from docetaxel, that the reduction in ctDNA supports the drug as active in NSCLC, and that KRAS, TP53, STK11 and KEAP1 mutations are negative prognostic factors in patients treated in the second line. The authors describe the work as an exploratory analysis, so the findings are hypothesis-generating rather than practice-defining.
Sources
- Cancer Research Communications. Evaluation of Biomarkers for Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer: Insights From the EVOKE-01 Study (2026-07-14). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Giannis Mountzios.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
