Phase 1 trial of SHR-A2102, a nectin-4–directed antibody drug conjugate (ADC), in advanced solid tumors.

107 Background: Nectin-4 is a cell adhesion molecule that is highly expressed in a wide variety of cancers and is associated with poor prognosis. SHR-A2102 is a novel ADC consisting of a fully humanized Nectin-4–directed monoclonal antibody, bound to topoisomerase I inhibitor payload via a cleavable linker. We conducted a multi-center, phase 1 trial to evaluate SHR-A2102 in advanced solid tumors. Methods: Patients (pts) with Nectin-4 positive, locally advanced unresectable or metastatic solid tumors were enrolled. The study included dose-escalation (D-ESC), dose-expansion (D-EXP) and efficacy-expansion (E-EXP) phases. SHR-A2102 was given IV at 2–10 mg/kg, Q3W during D-ESC, and at 6 mg/kg and 8 mg/kg Q3W during D-EXP and E-EXP. The primary objectives were to assess safety and tolerability. Results: As of Dec. 20, 2024,369 pts were enrolled and treated (median age, 59 y; ECOG PS 1, 85.6%; ≥2 lines of prior therapy, 64.0%). During D-ESC, DLT occurred in 1 pt (10 mg/kg; grade 4 decreased platelet count). Overall, grade ≥3 TRAEs occurred in 167 (45.3%) pts, with the most common (≥3%) being decreased neutrophil count (25.5%), decreased white blood cell count (16.3%), anaemia (11.7%), decreased lymphocyte count (8.7%), decreased platelet count (4.9%), asthenia (3.5%) and nausea (3.3%). 2 (0.5%) pts discontinued treatment due to TRAE. ILD occurred in 1 (0.3%; grade 3) pt. In 304 evaluable pts for response, ORR was 35.2% (95% CI 29.8-40.9) and DCR was 84.2% (95% CI 79.6-88.1). As of data cutoff, 146 (39.6%) pts had disease progression or died; median PFS was 4.7 mo (95% CI 4.3-5.6). Efficacy in selected tumor types is shown in Table. Conclusions: SHR-A2102 demonstrated a manageable safety profile and promising activity across a variety of pretreated advanced solid tumors. Multiple trials are ongoing to further assess SHR-A2102 both as monotherapy and in combination therapy for solid tumors. Clinical trial information: NCT05701709 . Efficacy in selected tumor types (efficacy evaluable set). EGFR -mut Nsq NSCLC (N=69) EGFR -wt Nsq NSCLC (N=44) Sq NSCLC (N=44) HR+/HER2-BC (N=20) TNBC (N=32) HNSCC (N=12) All patients † (N=304) Best overall response, n (%) CR * 0 1 (2.3) 0 0 0 0 1 (0.3) PR * 30 (43.5) 10 (22.7) 11 (25.0) 13 (65.0) 18 (56.3) 6 (50.0) 106 (34.9) SD 28 (40.6) 21 (47.7) 33 (75.0) 4 (20.0) 9 (28.1) 5 (41.7) 149 (49.0) PD 11 (15.9) 11 (25.0) 0 3 (15.0) 5 (15.6) 1 (8.3) 47 (15.5) Not evaluable 0 1 (2.3) 0 0 0 0 1 (0.3) ORR * , % (95% CI) 43.5 (31.6-56.0) 25.0 (13.2-40.3) 25.0 (13.2-40.3) 65.0 (40.8-84.6) 56.3 (37.7-73.6) 50.0 (21.1-78.9) 35.2 (29.8-40.9) DCR, % (95% CI) 84.1 (73.3-91.8) 72.7 (57.2- 85.0) 100.0 (92.0-100.0) 85.0 (62.1-96.8) 84.4 (67.2-94.7) 91.7 (61.5-99.8) 84.2 (79.6-88.1)