Notes
BT-062: chimeric (hinge-unmodified) human IgG4 anti-CD138/syndecan-1 antibody (nBT062, chimerized from murine B-B4) conjugated to maytansinoid DM4 via SPDB disulfide linker at random lysines; DAR 3-4 per ADCdb (3.5 used as midpoint). Program (Biotest): two monotherapy Ph1 studies pooled in Kelly CLML 2019 (n=67 total: single-dose q3w NCT00723359 n=32, MTD 160 mg/m2; multi-dose D1,8,15 q4w n=35, MTD/RP2D 140 mg/m2) PLUS Ph1/2a combination NCT01638936 (n=64; indatuximab ravtansine + low-dose dexamethasone + lenalidomide [MTD 100 mg/m2] or pomalidomide [RP2D 100 mg/m2], D1,8,15 q4w). Program terminated.
OCULAR (reason for inclusion): NO aggregate ocular rate was published. Eaton 2015 (PMC4677113) and Kelly CLML 2019 describe 2 distinct patients, both at 160 mg/m2 (single-dose schedule NCT00723359): (A) a male patient with corneal epithelial damage + crystalline corneal inclusions, grade 2, 3 days after cycle 3; (B) a female patient with dry eye + blurred vision, grade 2, 4 days after cycle 4. Both events were grade 2 and 'medically significant'; reversibility/follow-up were explicitly NOT reported (per Eaton 2015). Off-target corneal toxicity typical of DM4 maytansinoids (CD138/syndecan-1 is not expressed on cornea; SPDB-DM4 class, cf. mirvetuximab/anetumab/tusamitamab/coltuximab). The ocular percentages (oae_any 6.3%, ae_corneal/dry_eye/blurred_vision 3.1% each) are DERIVED lower bounds (2 distinct pts and 1 pt per PT, against the single-dose study population N=32); the source states only counts, not rates, and the 160 mg/m2 cohort-specific rate is HIGHER because not all 32 received 160 mg/m2 (the 160 cohort N was not separately reported). oae_g3plus_pct left blank: no G3+ ocular AE was reported (both documented events were G2), but these were spontaneously-reported AEs (no prospective ophthalmologic exam of all patients), so a true 0% G3+ is not established. CTCAE version not specified in accessible sources.
HEMATOLOGIC toxicity_rows are from the COMBINATION study (N=64, Lancet Haematol 2021) and are CONFOUNDED by the lenalidomide/pomalidomide + dexamethasone backbone (IMiD-driven cytopenias); NOT clean single-agent attribution -> tagged line_context >=2L (not RP2D) and excluded from the monotherapy RP2D summary slice. Monotherapy safety: 88% of AEs were grade 1-2, most common diarrhea + fatigue (no percentages published in accessible sources -> GI/Hepatic/Pulmonary/Neurologic-PN/Infusion summary rows omitted rather than fabricated). Combo ORR: +lenalidomide 71.7% (33/46), +pomalidomide 70.6% (12/17).
CHEMISTRY: linker LIN0VZYER (SPDB) physchem (SMILES/formula/MW 326.399/TPSA 76.57/xLogP 2.2093) identical to the existing SPDB-DM4 DB rows. DM4 payload physchem = DB-standard maytansinoid values (tier C). linker_plasma_t_half not measured for indatuximab specifically (SPDB-DM4 class ~5.5-7 d) -> left blank. Released catabolite and cleavage mechanism are class-inferred (SPDB disulfide reductively cleaved -> DM4 / S-methyl-DM4). IgG4 isotype chosen for low effector function (Ikeda CCR 2009). Cross-ref IDs: DrugBank DB16195; PubChem SID 472423471/223370377/160671957.