Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability · source-verified
Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry
Identifiers, registry & notes
ADC id
lorvotuzumab-mertansine
Approval status
Discontinued
Approval year
-
UniProt
P13591
ADCdb ADC
DRG0SDZSF
ADCdb antibody
ANI0VELIR
ADCdb target
TAR0YOEAI
Primary source
Shah et al. Invest New Drugs 2016;34(3):290-9 (IMGN901 Ph1, CD56+ solid tumors; PMID 26961907); ocular per Eaton et al. ADC ocular-AE review (PMC4677113)
Composition/linker/payload IDs from ADCdb DRG0SDZSF and linker LIN0QDUUQ. IMPORTANT: ADCdb lists conjugation as "Random Cysteines," but SPP (N-succinimidyl 4-(2-pyridyldithio)pentanoate) is an NHS-ester linker that conjugates to antibody LYSINE residues (the 2-pyridyldithio group then forms the cleavable disulfide to DM1's thiol); the alias "IMGN901-TAP" confirms ImmunoGen's lysine-linked maytansinoid (TAP) platform. Recorded here as Conventional Lys conjugation (chemically correct and consistent with the DB's other maytansinoid rows); the ADCdb "Random Cysteines" annotation appears to be an error. Linker is a hindered (alpha-methyl) disulfide -> cleavable/reductive (GSH). Because it is cleavable, the released species is free DM1 / S-methyl-DM1 (partial bystander), so FREE-DM1 physchem is used (MW 738.3), NOT the charged Lys-SMCC-DM1 catabolite values (MW 1103.7) used for the non-cleavable T-DM1.
Clinical data: Phase I CD56+ solid-tumor study, Shah MH et al., Invest New Drugs 2016;34(3):290-9 (PMID 26961907; PMC4859861; DOI 10.1007/s10637-016-0336-9). IV days 1-3 every 21 days (fractionated); dose 4-94 mg/m2/day; MTD 75 mg/m2; RP2D 60 mg/m2 (n=38 in expansion); safety population N=97 (52 escalation + 45 expansion); CTCAE v4.0. Reported rates are pooled over n=97 (the publication does not break out AE rates by dose), so the "RP2D" line_context flags the primary/headline cohort while the n column carries the n=97 denominator.
OCULAR (reason for inclusion): (1) Eye redness <=G1-2 in 3/64 (4.7%) at three dose levels, per the Eaton ADC ocular-AE review (PMC4677113) citing the IMGN901 solid-tumor dose-escalation (n=64). This denominator differs from the n=97 full publication, which did not separately tabulate eye redness. (2) One RPLS-associated reversible cortical blindness at the 60 mg/m2 RP2D (1/97; bilateral parieto-occipital MRI lesions; CNS-mediated; causality to IMGN901 unverifiable per authors; residual visual field deficit). No keratopathy/conjunctivitis/dry eye/blurred vision reported - unlike classic DM4 maytansinoid corneal toxicity, this DM1 ADC shows only low-grade nonspecific surface eye redness plus a single neuro-ocular event. oae_g3plus_pct=0 refers to the ophthalmic-surface OAE (eye redness, all G1-2); the RPLS cortical blindness (G3+ visual) is captured as a separate toxicity row. ocular_surface_subtype="Mixed" reflects the surface (eye redness) + visual (cortical blindness) signals; neither is a classic corneal keratopathy.
HEMATOLOGIC: the verified primary publication did NOT quantify anemia/neutropenia/thrombocytopenia (those PT words are absent; no patient met the grade-4 neutropenia DLT). Only a 7.2% "Blood and lymphatic system disorders" SOC aggregate is reported. A secondary web summary quoting anemia 55%/thrombocytopenia 48%/PN 52% directly contradicted the verified PN 17.5% and was excluded as unreliable.
OTHER: Headache 26.8% and "meningitis-like symptoms" were prominent (likely CD56/NCAM-related meningismus; managed with prophylactic steroids; among the DLTs) - noted here but not forced into the fixed organ-system rows. Most common Grade 3/4 TEAEs overall: hyponatraemia 8.2%, dyspnoea 8.2%, GGT 7.2%; 80.4% had any Grade 3/4 TEAE (37.1% treatment-related). No infusion-related anaphylaxis reported; no quantified infusion-reaction PT, so the Infusion organ system is left blank.
CAVEATS: payload_pka ~4.8 is taken from the DB's canonical free-DM1 value but appears low versus the structurally analogous DM4 thiol (~10.3) - possible DB reference typo; flagged. Antibody isotype IgG1 and origin Humanized are from established huN901/lorvotuzumab nomenclature (the "-zumab" stem; humanized murine N901), not explicitly stated in the fetched sources -> tier C for those two fields. Program discontinued (ADCdb: "Phase 2 (Terminated)").