Notes
AMG-224 (Amgen): anti-BCMA (TNFRSF17) human IgG1 conjugated to DM1 (mertansine, maytansinoid microtubule inhibitor) via a NON-CLEAVABLE MCC/SMCC thioether linker through antibody lysine residues (same chemistry as T-DM1). DAR not publicly disclosed (ADCdb, ADC Review, and primary letter all omit it). Phase 1 first-in-human NCT02561962 in relapsed/refractory multiple myeloma: 42 enrolled, 40 in safety analysis set (~21-29 dose-escalation across 7 flat-dose levels 30-250 mg [Doses A-G], 11 in dose-expansion at 3 mg/kg [Dose H]). MTD = 190 mg flat IV Q3W (approximately 3 mg/kg); expansion at 3 mg/kg Q3W. ORR 23% (9/40), median DOR 14.7 months. Program deprioritized July 2017 in favor of Amgen BiTE platform; CT.gov status Completed.
QUALIFYING OCULAR DATUM: treatment-emergent ocular AEs grade 1-2 in 30% of patients, no grade >=3, no keratopathy/visual-acuity loss, and crucially NO dose reduction/delay/discontinuation due to ocular toxicity - explicitly contrasted as favorable vs belantamab mafodotin (46% dose-reduced for ocular). One systematic review (PMC12774553) cites 21% (possibly treatment-related-only), reconciled in the toxicity row notes. Specific ocular preferred terms are not disclosed publicly, so ocular_surface_subtype = Unknown (cannot confirm corneal despite maytansinoid class, because keratopathy was explicitly absent).
OTHER TOXICITY: thrombocytopenia is the dominant toxicity (treatment-related grade >=3 40%; grade 4 24%); anemia 21%. Neutropenia, fatigue, nausea, and AST increase were also noted among common grade >=3 events but without extractable percentages, so no rows were created for them (blank = not in accessible literature). Peripheral neuropathy not prominent (consistent with non-cleavable DM1 / T-DM1-like profile).
SOURCING CAVEAT: the primary publication (Lee et al., Leukemia 2021;35:255-258) is paywalled and PubMed shows 'no abstract'; all efficacy/toxicity figures were obtained via the curated review PMC10137208 (best_source), the BCMA-ADC systematic review PMC12774553, ADC Review drugmap, and the NCT02561962 posted-results module (CT.gov API v2). Composition and dosing are tier B (registry + curated concordant sources); ocular and other toxicity rows are tier C (secondary, primary inaccessible). DM1 physicochemistry is standard shared-payload data from PubChem CID 11343137 (MW 738.3, formula C35H48ClN3O10S, XLogP 2.2, TPSA 157, formal charge 0; non-bystander due to charged lys-MCC-DM1 catabolite). ADCdb did not disclose a linker (LIN) id or any linker physchem for this entry, so the adcdb linker fields are left blank.