DXC006, a first-in-class CD56-targeting antibody-drug conjugate, in advanced solid tumors: A first-in-human, phase I dose escalation clinical trial.

Abstract

3000 Background: DXC006 is an antibody-drug conjugate of a humanized anti-CD56 antibody linked to the topoisomerase I inhibitor CPT113 with DAR=4 through a cleavable peptidyl bis-linker by CrossConju technology. DXC006 demonstrated strong antitumor activity in vivo and in vitro , here we report the safety and preliminary efficacy of first-in-human phase I trial of DXC006. Methods: Patients with metastatic/locally advanced solid tumors after at least one line of systemic standard therapy were enrolled. For dose escalation (D-ESC), DXC006 was administered intravenously at doses of 1.2, 2.4, 4.8, 6.0mg/kg Q2W or 6.0, 7.2 mg/kg Q3W with BOIN design and 3+3 design. A subset of pts was enrolled into dose-expansion (D-EXP) at recommended dose regimen. The primary objectives were to evaluate the safety and tolerability (dose limiting toxicities, DLTs; maximum tolerated dose, MTD) of DXC006. Results: Data cutoff at December 26 th , 2025, 72 patients were enrolled and received at least one dose(D-ESC n=16,D-EXP n=56)，including SCLC (n=44), lung adenocarcinoma (n=11), lung squamous cell carcinoma (n=3), neuroendocrine neoplasm (n=14). No DLTs occurred and MTD was not reached. D-EXP was carried out at 4.8mg/kg Q2W and 6.0mg/kg Q3W regimens. Treatment related adverse events (TRAEs) rate (all grade/≥G3) was 97.2% and 27.8%, TOP5 most common TRAEs (all grade/≥G3) were decreased appetite (54.2%/0%), nausea (52.8%/0%), anemia (48.6%/20.8%), asthenia (37.5%/1.4%), sensory disturbance (33.3%/0%). No interstitial lung disease (ILD) was observed. TRAEs led to dose interruption/discontinuation were observed in (23.6%/1.4%) of the patients. RP2D is 6.0mg/kg Q3W. Totally, 59 patients were eligible for efficacy analysis. For all patients, the objective response rate (ORR) and disease control rate (DCR) were 52.5 % and 81.4% (including confirmed and pending confirmation PR); for SCLC patients, were 69.4% and 91.7%; for lung adenocarcinoma, were 45.5% and 72.7% (details in table). Encouraging anti-tumor activity was observed for DXC006 treatment in SCLC at 2nd line (ORR 85.7%, confirmed 64.3%). PK, PD and PFS results will be updated in the upcoming meeting. Conclusions: DXC006 demonstrated a manageable safety profile and adequate tolerability, and showed encouraging efficacy in pretreated advanced solid tumors, especially in SCLC. Clinical trial information: NCT06224855 . Small cell lung cancer Small cell lung cancer（2nd Line） Neuroendocrine Neoplasm Lung Adenocarcinoma Lung Squamous cell carcinoma N 36 14 10 11 2 Median prior treatment line (range) 2(1, 6) 1(1, 1) 2(1, 6)　 2(1, 3)　 5(5, 5)　 cPR 14 9 1 4 0 PR 25 12 1 5 0 SD 8 2 6 3 0 PD 3 0 3 3 2 ORR % (95% CI) 69.4 (53.1, 82.0) 85.7 (60.0, 96.0) 10.0 (1.8, 40.4) 45.5 (21.3, 72.0) 0.0 DCR % (95% CI) 91.7 (78.2, 97.1) 100 (78.5, 100) 70.0 (40.0, 89.2) 72.7 (43.4, 90.3) 0.0