No payload IC50 reported on the ADCdb ADC page. ADCdb reports clinical efficacy for the ADC: objective response rate 0.00%, with stable disease in 11 of 29 patients (37.90%).
06
Dosing & regimen
Dosing
RP2D dose
Not established; MTD not reached (2.4 mg/kg highest tolerated; doses 0.15-4.8 mg/kg explored; study terminated early)
King et al., Invest New Drugs 2018 (PMID 29333575; PMC7519583); ClinicalTrials.gov NCT02122146 posted results
Aliases & development codes
anti-Trop-2/Aur0101 ADC
Notes
PF-06664178 (Pfizer) = humanized anti-Trop-2 (TACSTD2) IgG1 mAb PF-06478924 conjugated to the auristatin Aur0101 (PF-06380101, a dolastatin-10 analogue) via a cleavable cathepsin-B AcLys-Val-Cit-PABC linker (ADCdb LIN0FSRSR), DAR 2, random interchain-cysteine conjugation. Phase 1 dose-escalation NCT02122146 (N=31; 0.15-4.8 mg/kg IV Q3W); TERMINATED early for excess toxicity. MTD/RP2D NOT reached (2.4 mg/kg was highest tolerated; 3.6/4.2/4.8 mg/kg intolerable).
DOMINANT/DOSE-LIMITING TOXICITY was SKIN RASH (8/31 = 25.8% any-grade [pub ~26%]; Grade 3+ in 5 patients including a Grade 4 toxic epidermal necrolysis and a Grade 4/serious bullous dermatitis), together with neutropenia and mucosal inflammation. Skin is NOT in the organ-system enum so no skin toxicity_row was created; it is recorded here as it is the principal toxicity. All-causality Grade 3/4 AEs occurred in 20/31 (64.5%); treatment-related in 14/31 (45.2%).
OCULAR (the flagged reason for inclusion) is MINIMAL and ALL-CAUSE: vision blurred 6.5% (2/31), dry eye 3.2% (1/31), conjunctival hyperaemia 3.2% (1/31) — all non-serious, no Grade 3+, no corneal/keratopathy/keratitis. King et al. 2018 EXPLICITLY state 'No ophthalmologic toxicity was observed in the evaluable patients,' i.e., these CT.gov eye PTs are background/incidental, NOT treatment-attributed. Hence ocular tier C and overall_tier C for the OAE outcome. CT.gov assessment type for these PTs is NON_SYSTEMATIC. Per-dose all-cause distribution: vision blurred at 1.20 mg/kg (1/4) and 4.80 mg/kg (1/8); dry eye and conjunctival hyperaemia each 1/8 at 4.80 mg/kg only — no dose-OAE relationship, so dose_oae_available=false. This is a useful LOW/negative ocular reference case for an auristatin (Aur0101) ADC at low DAR (2).
HEPATIC: no ALT/AST/bilirubin AEs reported (a single 'hepatic encephalopathy' event was disease/liver-related, not transaminitis) — no hepatic toxicity_row created (blank = not in literature).
PAYLOAD Aur0101 = PF-06380101 (PubChem CID 71569947, C39H62N6O6S): MW 743.0, XLogP3 4.1, TPSA 184; neutral/lipophilic, membrane-permeable -> bystander-capable like MMAE; one basic primary aliphatic amine (no acidic groups) -> +1 net charge at pH 7.4; logD7.4 and experimental pKa not in sources. Aur0101 is NOT one of the standardized shared payloads, so values are PubChem-computed (tier C). The same payload is used in Pfizer's PF-06650808 and PF-06804103.
CTCAE version not specified in accessible sources (CTCAE assumed; likely v4.0 for this 2014-2016 trial). pct values computed from CT.gov Total-group counts (denominator 31); percentages match the wave1 oae_hint exactly. Composition/dosing/non-ocular toxicity are tier B (peer-reviewed King et al. 2018 corroborated by CT.gov posted results); linker chemistry and payload physchem are tier C (ADCdb/PubChem secondary).