SHR-1826, a c-MET directed antibody-drug conjugate (ADC), in advanced solid tumors: Updates from a phase 1 study.

Abstract

8525 Background: SHR-1826 is a novel ADC comprising a humanized IgG2 monoclonal antibody targeting c-MET, conjugated via a cleavable peptide-based linker to a topoisomerase I inhibitor payload. We conducted a multi-center, first-in-human, phase 1 trial of SHR-1826 in patients with advanced solid tumors. Here we report updated results, with a focus on patients with EGFR -mutated ( EGFRmut ) lung adenocarcinoma (LUAD). Methods: The study consisted of dose-escalation (i3+3 design), dose-expansion and efficacy-expansion phases. Patients with advanced solid tumors harboring MET alterations, who had failed standard therapy or had no available standard treatment options, were enrolled and received SHR-1826 intravenously at 2.2–6.0 mg/kg Q3W. In patients with EGFRmut LUAD, 4.0 and 5.0 mg/kg Q3W were evaluated during dose and efficacy expansion. Results: As of Dec. 3, 2025, 195 patients with lung (n=126), colorectal (n=40), gastric (n=22), liver (n=5), or pancreatic (n=2) cancer were treated. Median age was 59.0 yrs; 89.7% had ECOG performance status 1. Among 36 patients with EGFRmut LUAD, median number of prior lines of therapy was 2 (range 1–9); 97.2% had previously received EGFR-TKI (3 rd generation, 88.9%) and 75.0% received platinum-based chemotherapy. As of data cutoff, median follow-up was 14.4 months. Efficacy in EGFRmut LUAD across doses is shown in Table 1. Overall, the confirmed objective response rate (ORR) was 41.7% (95% CI 25.5–59.2) and median duration of response (DoR) was 14.1 months (95% CI 5.6–not reached [NR]). Median progression-free survival (PFS) was 9.8 mo (95% CI 5.8–15.4). Median overall survival (OS) was not reached; 12-month OS rate was 67.4% (95% CI 48.9–80.5). In all 195 patients, grade ≥3 treatment-related adverse events (TRAEs) were reported in 129 patients (66.2%), with all occurring in ≥5% being hematological toxicities. Interstitial lung disease occurred in 4 (3.1%; grade ≥3, n=2 [1.6%]) patients. TRAEs led to treatment discontinuation in 8 (4.1%) patients. No treatment-related deaths were reported. Conclusions: SHR-1826 demonstrated encouraging activity with manageable safety in heavily pretreated patients with MET-altered EGFRmut LUAD. Multiple trials are ongoing to assess SHR-1826 combined with other anti-tumor therapies in NSCLC. Clinical trial information: NCT06094556 . Efficacy outcomes in EGFRmut LUAD. 4.0 mg/kg (n=16) 5.0 mg/g (n=18) All patients (n=36) Confirmed ORR (n/N; 95% CI), % 31.3 (5/16; 11.0–58.7) 50.0 (9/18; 26.0–74.0) 41.7 (15/36; 25.5–59.2) DCR (n/N; 95% CI), % 87.5 (14/16; 61.7–98.4) 100.0 (18/18; 81.5–100.0) 94.4 (34/36; 81.3–99.3) Median DoR (95% CI), mo NR (8.6–NR) 9.7 (4.2–NR) 14.1 (5.6–NR) Median PFS (95% CI), mo 12.4 (2.6–NR) 8.4 (4.5–15.4) 9.8 (5.8–15.4) 12-mo OS (95% CI), % 67.0 (37.9–84.7) 69.1 (40.7–85.9) 67.4 (48.9–80.5) Data are based on the full analysis set. DCR, disease control rate.