Notes
ADC: Vobramitamab duocarmazine (MGC018 / vobra duo), MacroGenics anti-B7-H3 (CD276) humanized IgG1 ADC with a Byondis-derived vc-seco-DUBA duocarmycin (DNA-alkylating) payload, DAR ~2.7. Linker LIN0HGTZQ and payload seco-DUBA (PAY0SOSMQ) are SHARED with trastuzumab-duocarmazine (DRG0THGAW) already in the DB; linker SMILES/formula/MW/TPSA/xLogP and payload physchem are taken from that shared chemistry.
CONJUGATION DISCREPANCY: ADCdb lists conjugation/site as "Random Lysines," which is inconsistent with the maleimide ("Mal-PEG2-Val-Cit-PABA") linker and the shared Byondis vc-seco-DUBA platform. A maleimide attaches to interchain cysteine thiols, so I report conjugation as interchain Cys (maleimide), matching trastuzumab-duocarmazine. Flag for reconciliation.
RP2D / DOSE SELECTION: TAMARACK (NCT05551117) is a randomized Phase 2 dose-optimization in mCRPC testing 2.0 mg/kg Q4W (ITT n=91) vs 2.7 mg/kg Q4W (ITT n=90); CT.gov safety populations N=90 and N=86. 2.7 mg/kg gave higher confirmed ORR (41% vs 20%) and was the dose carried into the Part 2 expansion, so I designate RP2D = 2.7 mg/kg Q4W (primary cohort = Part 1 Arm B, N=86, line_context=RP2D); the 2.0 mg/kg arm is included as comparator rows. NOTE: the 2.0 mg/kg arm was clearly better tolerated (fewer effusions, PPE, cytopenias), and MacroGenics suggested mitigation via longer interval (e.g. Q6W) or loading dose. The Phase 1 (CP-MGC018-01, NCT03729596) RP2D was 3.0 mg/kg Q3W. The entire program was DISCONTINUED on 2024-07-23 (remaining n=32 stopped) and TAMARACK is TERMINATED, on the totality of efficacy + emerging safety.
OCULAR (priority): Best source is the ClinicalTrials.gov posted results (final, MedDRA 27.1, >=5% threshold) - more complete than the paywalled ESMO 2024 poster 1654P. At RP2D (2.7 mg/kg): conjunctivitis 19.8% (17/86, the max ocular PT -> oae_any_pct=19.8), dry eye 11.6%, eyelid oedema 10.5%, lacrimation increased 5.8%; at 2.0 mg/kg: conjunctivitis 12.2%, dry eye 11.1%, eyelid oedema 6.7%, lacrimation 5.6%. Keratitis, blurred vision and photophobia were each <5% (below threshold) despite being protocol-monitored AESIs with mandatory prophylactic eye drops (corticosteroid/antihistamine/artificial tears TID), no-contact-lens and lid-hygiene instructions, and dose hold/reduce/discontinue rules. Only 1 serious ocular event in the whole trial (1 serious dry eye, 2.0 mg/kg arm); ocular AEs were low-grade (ESMO 2024: AEs >=10% were mostly grade 1-2). ocular_surface_subtype set to "Mixed" (conjunctival + ocular-surface + eyelid, without corneal keratopathy or visual-acuity loss); this differs from the corneal-microcyst pattern of MMAF/maytansinoid ADCs. oae_g3plus_pct left blank (registry gives serious/non-serious, not CTCAE grade; no explicit G3+ ocular count published). NOTE the ocular signal is more apparent in TAMARACK Phase 2 than in the Phase 1 poster (where ocular AEs were not in the >=10% TRAE table, i.e. <10%).
GRADE DATA CAVEAT: CT.gov posted results report AEs split into Serious vs Other(non-serious, >=5%) categories, NOT by CTCAE grade. All toxicity_rows therefore use grade_bucket="Any" with the non-serious >=5% incidence as the headline figure; material serious-AE counts are given in the row notes. Pleural effusion is reported at the ESMO 2024 any-grade values (44.2% at 2.7 mg/kg; 28.8% at 2.0 mg/kg; tier D) because the registry split (non-serious 33.7%/27.8% + serious 14.0%/7.8%) understates the true any-grade union. Overall Grade >=3 TEAE rate was >50% (ESMO 2024).
HALLMARK TOXICITIES not in the organ_system enum: pericardial effusion (serosal; pooled TAMARACK 15.3%; 2.7 mg/kg non-serious 15.1% + serious 5.8%; 2.0 mg/kg 14.4% + 1.1%) and palmar-plantar erythrodysaesthesia (PPE) syndrome (2.7 mg/kg 27.9% (24/86); 2.0 mg/kg 21.1% (19/90); pooled 23.3%). Also prominent: asthenia (2.7 mg/kg 60.5%, 2.0 mg/kg 52.2%), peripheral oedema (40.7%/36.7%), decreased appetite (40.7%/36.7%), fatigue (23.3%/27.8%). Pericardial/pleural effusions were the doses-limiting serosal-toxicity theme that, with fatal pneumonitis, drove the program's discontinuation.
Sources: ADCdb DRG0DEGEG and linker LIN0HGTZQ (idrblab.net); ClinicalTrials.gov NCT05551117 (TAMARACK) posted results (authoritative AE source); MacroGenics ESMO 2024 abstract 1654P via UroToday/MacroGenics coverage; Shenderov et al., ESMO 2021 poster 620P, MGC018 Phase 1 cohort expansion (NCT03729596); shared seco-DUBA/vc-seco-DUBA chemistry per trastuzumab-duocarmazine DB row.