Notes
EFNA4 (Ephrin-A4)-targeted ADC; antibody huE22 (humanized IgG1); linker AcButDMH (acid-labile hydrazone + disulfide; ADCdb LIN0KWKDL, the SAME shared calicheamicin linker as gemtuzumab-ozogamicin, inotuzumab-ozogamicin, and CMD-193); payload N-acetyl-gamma-calicheamicin (enediyne, DNA double-strand breaks); DAR 4.6 (ADCdb); random-lysine conjugation; Pfizer. Phase 1 FIH NCT02078752 (Garrido-Laguna et al., Int J Cancer 2019;145(7):1798-1808, PMID 30680712), advanced solid tumors with a metastatic-TNBC dose-expansion; development discontinued (Phase 1 terminated). RP2D 0.015 mg/kg QW; MTD not reached for either Q3W or QW; 1 DLT (thrombocytopenia) on QW.
OCULAR — CRITICAL ATTRIBUTION CAVEAT: the ocular AEs are ALL-CAUSALITY events from the ClinicalTrials.gov posted results, NOT treatment-related. The peer-reviewed publication's treatment-related AE tables (Tables 3-4) contain ZERO ocular events. Calicheamicin is not a classically ocular-toxic payload (gemtuzumab/inotuzumab report 0% ocular AEs in their FDA labels). These eye AEs are almost certainly background/incidental in an advanced-cancer population; causal attribution to PF-06647263 is weak. No ocular AE was serious or Grade >=3 (CT.gov serious-AE table has zero eye disorders; the paper lists no ocular event among Grade 3/4 AEs) -> oae_g3plus_pct=0 is a documented zero.
CORRECTION to the screening hint: the hint's 'conjunctivitis 5.0%' is NOT an Eye-disorders SOC ocular-surface event -- it is 'Conjunctivitis' under the Infections & infestations SOC (infective conjunctivitis, 3/60: groups EG001/EG007/EG008), not a drug-induced ocular toxicity. The only Eye-disorders conjunctival PT is conjunctival haemorrhage (1/60, 1.7%, a hemorrhagic event likely related to thrombocytopenia). Hence ae_conjunctival_pct is left blank (no on-target conjunctivitis).
DENOMINATOR NOTE: the CT.gov AE table is split into 10 dose-level groups (no pooled column). RP2D = 0.015 mg/kg QW = EG001 (Part 1, n=13) + EG009 (Part 2 TNBC expansion, n=12) = n=25. ocular{} summary and all line_context=RP2D rows use this n=25 all-causality slice (tier D, no grade resolution at this cohort). Treatment-related grade data (tier B) live in line_context=dose-escalation rows (Q3W arm n=25; QW arm n=35). Per-group RP2D ocular detail: 0.015 QW Part 1 (n=13) vision blurred 15.4%, dry eye/eye irritation/iritis/mydriasis 7.7% each; 0.015 QW Part 2 (n=12) dry eye/cataract/diplopia 8.3% each. Whole-study pooled all-cause (N=60) ocular: dry eye 10.0%, lacrimation increased 10.0%, vision blurred 6.7%, eye irritation 3.3%, ocular hyperaemia 3.3%; iritis/cataract/diplopia/conjunctival haemorrhage/mydriasis/vitreous floaters/eye discharge/eye haemorrhage/eye pruritus/eye symptom 1.7% each.
NON-OCULAR (Garrido-Laguna 2019, treatment-related): dominant toxicities are thrombocytopenia (QW 31.4% any/5.7% G3+; Q3W 44% any/20% G3+ [G3 8% + G4 12%]), GI (nausea/vomiting/diarrhea/mucositis 20-64%; G3+ rare: Q3W vomiting 4%, QW nausea 2.9%, QW gastritis G4 2.9%), and the calicheamicin-class hepatobiliary signal (Q3W Grade-3 hyperbilirubinemia 8%; 1 grade-1 hepatic VOD + 1 nodular regenerative hyperplasia/portal hypertension in the Q3W arm; pooled all-cause VOD 1.7%, blood bilirubin increased 11.7%, AST increased 10%). Neutropenia infrequent (~1.7-5% pooled), consistent with attenuated marrow toxicity in a solid-tumor (non-hematologic-target) setting vs gemtuzumab/inotuzumab. Peripheral neuropathy 10% pooled all-cause/low-grade (not a calicheamicin toxicity). No drug-related ILD/pneumonitis (1 'radiation pneumonitis' = radiotherapy-related) and no infusion-related reactions reported -> pulm_ild and infusion left BLANK (not zero).
Linker physchem (SMILES/formula/MW 221.256/TPSA 69.39/xLogP 1.5335) carried from the shared LIN0KWKDL platform (verified on the ADCdb linker page, shared with gemtuzumab/inotuzumab/CMD-193). payload_physchem uses the standard calicheamicin-gamma1 reference values (shared payload) per DB convention. Derived columns (dna_damage subtype, FcgammaR/C1q status, stability conditional/unconditional, severity, HCA/HPA) intentionally left blank for downstream computation.