Notes
IDENTITY: SYS6002 = CRB-701 (same molecule). Nectin-4-targeting ADC; MMAE payload; DAR 2 homogeneous; site-specific microbial-transglutaminase (glutamine-directed) conjugation; NH2-PEG3-Val-Cit-PABC cathepsin-B cleavable linker. CSPC Jushi Biomedicine (SYS6002, China study SYS6002-001) licensed ex-China to Corbus Pharmaceuticals (CRB-701, NCT06265727). Explicitly engineered to lower circulating free-MMAE (and thus the PN/rash dose-limiting toxicities of enfortumab vedotin); poster Table 3 shows ~33% Cmax / ~29-68% AUC free-MMAE vs EV and a longer ADC half-life.
STUDY STRUCTURE: Two parallel Phase 1 programs. (1) China SYS6002-001 dose-escalation (BOIN; 0.2/0.6/1.2/1.8/2.7/3.6/4.5 mg/kg Q3W IV; N=37 by ASCO-GU 2025; NO ocular prophylaxis). (2) Western US/UK Phase 1/2 (NCT06265727; N=38 by ASCO-GU 2025; WITH a proactive preventative ocular-toxicity protocol). Combined N=75 (ASCO-GU 2025). ESMO 2025 (967P, Sep-1-2025 cut): 167 enrolled / 122 evaluable (HNSCC n=41, cervical n=37, mUC n=23, other n=21); grade >=3 AEs ~30%. No DLTs in escalation; most AEs G1/2. Dose optimization at 2.7 & 3.6 mg/kg; RP2D expected Q4 2025 (not yet declared).
OCULAR (qualifying reason): Corneal epithelial lesions and dry eye are the PRINCIPAL toxicities (off-target corneal, EV-like). Aggregate ocular AEs 66% (China, no prophylaxis) vs 38% (Western, with prophylaxis, at 2.7 & 3.6 mg/kg). Corneal epithelial lesions and dry eye each reported among grade 1/2 TRAEs occurring >20% (exact per-PT % NOT disclosed -> rows use 20 as imputed floor, tier D). 2 G3 corneal disorders (China, one each at 2.7 & 3.6 mg/kg); none at 4.5 mg/kg once preventative eye measures were introduced; 0 G3 ocular in Western with prophylaxis. >50% of patients had baseline corneal disorder/dry eye (attribution confounder).
NON-OCULAR: Anaemia is the most common non-ocular TEAE (>20% G1/2). Peripheral neuropathy low (4% combined, no G3+) and rash low/absent (China escalation reported none; combined skin 16%) -- the intended differentiation from EV. Lab AEs >20% (hypertriglyceridemia, hyponatremia, proteinuria, hematuria) are not mapped to the tracked organ-system buckets. Early China N=18 cut (Dec-2023): 1 pt with G3 ILD + G3 pulmonary-infection SAEs, and 1 separate pt with G3 ALT-increase SAE (captured as Pulmonary/Hepatic rows, tier D, early-cut denominator).
CAVEATS: Exact per-PT percentages for corneal lesions/dry eye/anaemia were only disclosed as ">20%" (rows imputed at 20, tier D). The 2 G3 corneal-disorder percentage uses China N=37 as an inferred denominator. ILD/ALT rows are from the early N=18 cut. CTCAE version not stated. Fc effector function appears RETAINED (poster figure: 'ADC + CDC functionality'), i.e., not effector-silenced; antibody isotype undisclosed (CDC implies likely IgG1). ascopubs/Annals full-text pages were 403-blocked; clinical data drawn from Corbus press releases, the publicly posted ASCO-GU 2024 poster PDF, and conference-coverage summaries. PubChem MMAE: MW 717.99, XLogP3 4.1, TPSA 150 (CID 11542188).