Comprehensive results of ESG401, a TROP2-targeting ADC: Updated phase 1 analysis in advanced solid tumors.

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1044 Background: ESG401 is a novel ADC comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to the Topoisomerase I inhibitor SN-38 via a stable cleavable linker. ESG401-101 is a phase 1, open-label, dose-escalation (1a) and dose-expansion(1b) study evaluating the safety and antitumor activity of ESG401 in advanced solid tumors. This report summarizes the comprehensive phase 1 results. Methods: Patients (pts) aged 18–75 years with locally advanced/metastatic solid tumors received ESG401 until unacceptable toxicity, progressive disease, or consent withdrawal. Phase 1a results (n = 40) have been reported previously. Phase Ib comprised three parallel cohorts: late-stage TNBC, late-stage HR+/HER2-, and first-line TNBC. Results: As of Oct 23, 2024, 156 pts were enrolled at 13 sites across China (40 in 1a; 116 in 1b). Most pts had metastatic HR+/HER2-BC (n = 65; median prior lines: 3; range: 1–10), followed by late-line TNBC (n = 47; median prior lines: 3; range: 1–12), first-line TNBC (n = 40), HER2+BC (n = 2), and one case each of endometrial cancer (EC) and adenoid cystic carcinoma (ACC). All pts had distant metastases at baseline; 13%, 57%, and 54% had brain, liver, and lung metastases, respectively. ESG401 demonstrated efficacy in pts with solid tumor(Table), including those with brain metastases. The safety profile remained consistent with no new or unexpected signals. The most common any-grade TEAEs were leukopenia, neutropenia, anemia, nausea, and vomiting. Grade ≥3 TRAEs were primarily neutropenia and leukopenia, none leading to permanent discontinuation. TRAEs led to delayed dosing, dose reduction, and discontinuation in 38.5%, 7.1%, and 2.6% of pts, respectively. Conclusions: ESG401 demonstrated favorable safety and efficacy benefits due to its enhanced linker, showing good safety and promising antitumor activity in advanced solid tumors across settings. These results warrant further clinical investigation. Clinical trial information: NCT04892342 . Late-line First-line HR+/HER2–BC TNBC HER2+BC EC ACC TNBC n 58 37 2 1 1 35 ORR% (95% CI) 34.5 (22.5, 48.1) 35.1 (20.2, 52.5) 0 0 0 83.0 (66.4, 93.4) DCR% (95% CI) 77.6 (64.7, 87.5) 62.2 (44.8, 77.5 100 100 100 100 (90.0, -) mPFS Mons (95% CI) 7.4 (4.0, 9.2) 3.7 (2.1, 4.9) 3.8, 21.3 a 8.3 b 3.7 b NR mDOR Mons (95% CI) 6.6 (4.6, 14.2) 4.5 (3.1, 13.6) NA NA NA NR a The actual value for these two patients is listed. b The actual value for one patient is listed. NA, not applicable. NR, not reached.

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