Abstract CT036: A first-in-human study result of a novel EGFR-targeted antibody drug conjugate (ADC) in patients with advanced nasopharyngeal carcinoma (NPC) (SYS6010-001-NPC)

Abstract Background: SYS6010 is a novel EGFR-targeted ADC, consisting of a humanized anti-EGFR mAb linked to a topoisomerase I inhibitor (JS-1) via a glycine̶̶-glycine-phenylalanine-glycine tetrapeptide linker (DAR = 8). This phase I study (ChiCTR2300072141) evaluated SYS6010 in advanced solid tumors, with NPC cohort results reported here following prior NSCLC data oral presentation on AACR 2025 (25-LB-9831-AACR). Methods: Patients with advanced NPC progressing after ≥1L prior therapy (including PD1 inhibitor and platinum-based chemotherapy) received SYS6010 at 4.2 or 4.8 mg/kg IV every 3 weeks (Q3W) until progression or intolerable toxicity. Primary endpoints were safety and tolerability; secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Subgroup analyses were conducted by prior EGFR monoclonal antibody treatment and therapy lines. Results: As of September 15, 2025 (data cutoff), 56 patients were enrolled in the safety population (4.2 mg/kg, n=34; 4.8 mg/kg, n=22). Median age was 49.5 years (range, 27-70); 83.9% were male; 19.6% had ECOG PS 0 and 80.4% PS 1; mean BMI was 22.7 ± 3.34; 30.4% had prior EGFR mAb therapy. All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs occurred in 64.3% (37/56) of patients, with a comparable incidence between the 4.2 mg/kg (64.7%) and 4.8 mg/kg (63.6%) groups. Most common Grade ≥3 TEAEs were hematological toxicities: white blood cell count decreased (33.9%), neutrophil count decreased (32.1%), and platelet count decreased (28.6%), and their median time of recovering to baseline or grade 1 was 5 days(d), 4 d and 10 d respectively. Non-hematological Grade ≥3 TEAEs were infrequent. As hematological toxicities are well manageable in clinical practice, so the TEAEs led to permanent drug withdrawal in only 7.1% (4/56) of patients, with dose reductions (39.3%) and interruptions (31.6%). In efficacy population (N=54), ORR was 31.5% (17/54), with rates of 28.1% (9/32) in 4.2 mg/kg group and 36.4% (8/22) in 4.8 mg/kg group, including 1 complete response in 4.2 mg/kg group, and DCR was 87.0% (47/54). Median PFS was 7.5 months (mo) (95% CI: 5.49, 8.38) and was consistent across dose groups (4.2 mg/kg: 7.4 mo; 4.8 mg/kg: 7.7 mo). Median OS was not reached, and the 12-mo OS rate was 66.4% (95% CI: 45.01, 81.00). Notably, in EGFR mAb-naive patients receiving ≥2nd line therapy, the ORR was 42.9% (6/14) for the 4.2 mg/kg dose and 50.0% (5/10) for the 4.8 mg/kg dose. The relationship between efficacy and biomarkers (Epstein-Barr virus status, EGFR expression level and so on) will be reported in future conference. Conclusions: SYS6010 demonstrated encouraging antitumor activity and manageable safety profile in advanced NPC patients, supporting further pivotal clinical development. Citation Format: Haiqiang Mai, Linquan Tang, Xicheng Wang, Shaojun Lin, Lei Liu, Runxiang Yang, Song Qu, Kunyu Yang, Yi Gong, Feng Liu, Yanhong Shang, Jinsheng Wu, Shaozhang Zhou, Mengxia Li, Jinheng Hao, Xiugao Yang, Xuechao Wan, Changming Xie, Ying Chen, Jiaxing Hao, Jing Yuan, Kai Zou, Chao Liu, Shun Lu. A first-in-human study result of a novel EGFR-targeted antibody drug conjugate (ADC) in patients with advanced nasopharyngeal carcinoma (NPC) (SYS6010-001-NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT036.