Notes
LY3076226 (IMC-D11): fully human anti-FGFR3 IgG1 (IMC-D11) conjugated to the maytansinoid DM4 via a reducible disulfide SPDB linker (random Lys / NHS ester). ADCdb ids: ADC DRG0XBJHU, antibody ANI0OKRWC, target TAR0ZNFNB (FGFR3), payload PAY0GTSVM (DM4), linker LIN0VZYER (SPDB, C13H14N2O4S2). The LIN0VZYER physchem (MW 326.399, TPSA 76.57, xLogP 2.2093) is identical to the SPDB entries already in the DB (anetumab-/tusamitamab-ravtansine). Linker labelled 'SPDB / sulfo-SPDB' per DB convention: ADCdb assigns plain SPDB (LIN0VZYER), while some LY3076226 literature describes sulfo-SPDB. DAR is genuinely undisclosed (ADCdb 'Undisclosed'; not in protocol or publication) -> left blank. DM4 payload physchem are the standard shared-payload values (PubChem CID 11686439 Ravtansine; matches existing DB DM4 rows).
CLINICAL (NCT02529553, single-arm Phase 1, terminated): 25 treated (Part A escalation 0.2/0.4/0.8/1.6/2.4/3.2/4.0/5.0 mg/kg, n=1,1,1,3,3,4,3,6; Part B expansion at 5.0 mg/kg in FGFR3-altered urothelial carcinoma, n=3). IV Q3W (D1 of 21-day cycle). No DLTs and MTD not reached; 5.0 mg/kg was the top/expansion dose. Only 2 treatment-related Grade 3 events (embolism; decreased platelet count); all other toxicities Grade 1-2. No responses.
DENOMINATOR / RP2D NOTE: there is no formal RP2D and per-cohort denominators are tiny (n=1-6), so all percentages and toxicity_rows are computed over the POOLED safety population N=25 (the trial's AE-table denominator: 'all participants who received at least one dose'); these pooled rows are tagged line_context='RP2D' per instruction as the primary analysis cohort, with the 5.0 mg/kg dose-level cohort = n=9 (6 escalation + 3 expansion). n_rp2d set to 25 to match the reported percentages. AE counts re-derived exactly from the raw ClinicalTrials.gov v2 JSON (not the summarizer). Grading per NCI CTCAE v4.0 (confirmed in protocol I7O-MC-JOBA); MedDRA 20.1; AE window up to 33 days post-treatment; events are all-cause TEAEs.
OCULAR (why this ADC qualifies): Eye-disorders SOC = vision blurred 3/25 (12%), keratitis 1/25, dry eye 1/25, corneal epithelial microcysts 1/25, photopsia 1/25, retinal pigment epitheliopathy 1/25. oae_any_pct=12.0 (max single PT = vision blurred). ae_corneal_pct=4.0 (max of keratitis/microcysts, each 1/25; union would be 8% across 2 patients). Classified Corneal (off-target) consistent with the DM4 maytansinoid microcystic-keratopathy signature and the DM4 family in the DB; note the SOC also contains a visual (photopsia) and a retinal (retinal pigment epitheliopathy) single-case finding. No ocular event was Grade >=3 (oae_g3plus_pct=0.0, inferred from the publication's complete G3 enumeration). LY3076226-specific ocular reversibility/recovery was not reported -> ae_reversibility left blank. dose_oae_available=True (per-dose-cohort OAE counts available).
Zero-valued rows (neutropenia, ILD/pneumonitis, infusion-related reaction) are documented absences from the complete AE listing (frequencyThreshold=0), tier C. payload_name kept as 'DM4 (free)' for DB consistency though ADCdb labels it 'Mertansine DM4'. ADC plasma t1/2 ~2-7 days (publication) recorded in linker_plasma_t_half.