Notes
PF-06650808 = humanized anti-Notch3 (NOTCH3) ADC, payload Aur0101 (auristatin 0101 / PF-06380101, a dolastatin-10 analog tubulin inhibitor that retains the thiazole ring and carries a free basic primary amine), cleavable Mc-Val-Cit-PABC linker, interchain-cysteine conjugation, DAR 4. Sponsor Pfizer. ADCdb DRG0WRFYU; linker LIN0SQEDQ; antibody ANI0UMBRJ; payload PAY0WDZAK; antigen TAR0PNBPC. Total-antibody analyte = PF-06460005.
CLINICAL: First-in-human Phase 1 NCT02129205 (Rosen et al., Invest New Drugs 2019, PMID 30887250), advanced solid tumors incl. TNBC, N=40, IV on Day 1 of each 21-day cycle (Q3W). Dose escalation 0.2-4.68 mg/kg (per CT.gov cohorts); MTD estimated 2.4 mg/kg (N=11 at that level); Part 2 expansion at 2.4 mg/kg enrolled 0 patients; study TERMINATED for sponsor reprioritization (recruitment suspended Feb 2017). CTCAE v4.03. Protocol DLTs were hematologic (e.g., Grade 4 neutropenia >7 d, febrile neutropenia) and non-heme Grade >=3; no DLTs at <=2.0 mg/kg. Top treatment-related AEs in the publication: fatigue 40.0%, decreased appetite 37.5%, nausea 35.0%, alopecia 32.5%, abdominal pain 25.0%, pruritus 25.0%, vomiting 25.0% (none ocular).
OCULAR (reason for inclusion): All ocular figures are ALL-CAUSE from CT.gov posted results (N=40); ocular AEs are NOT mentioned in the peer-reviewed paper -> tier C, causal attribution weak in an advanced-cancer population. Pooled: vision blurred 5.0% (2/40), conjunctivitis 5.0% (2/40, MedDRA Infections SOC), dry eye 2.5% (1/40), foreign-body sensation 2.5% (1/40). No ocular event appeared among serious AEs (no ocular SAE / no G3+ ocular reported; oae_g3plus left blank rather than asserting 0). DOSE STRATIFICATION (notable): at the MTD/RP2D 2.4 mg/kg cohort the ONLY ocular AE was conjunctivitis 2/11 (18.2%); the dry-eye, foreign-body-sensation and one blurred-vision case occurred at sub-MTD doses (0.4 and 2.0 mg/kg). Pooled N=40 reporting follows the wave1 oae_hint and the convention used for sibling Pfizer/Aur0101 ADC entries (PF-06263507, PF-06664178, PF-06804103). line_context tagged 'RP2D' to denote the primary/total safety population (no dedicated RP2D expansion exists); dose fields show the pooling explicitly.
CAVEATS/DERIVED: antibody_isotype left blank (not explicitly sourced; most likely humanized IgG1 cysteine-conjugate by class). payload_charge_pH7_4 '+1' is DERIVED from the free basic primary amine (PubChem formal charge 0); payload_pka and logD7.4 not available; payload_bystander left blank (vc-cleavable auristatin is plausibly bystander-capable, but the released free Aur0101 is cationic at pH 7.4, like MMAF -> no definitive source). Payload physchem from PubChem CID 71569947 (MW 743.0, XLogP3 4.1, TPSA 184, HBD 3, HBA 9). Linker physchem from ADCdb (C28H40N6O7, MW 572.663, TPSA 200.03, xLogP 0.6769); linker_smiles given as the clean canonical Mc-Val-Cit-PAB-OH. No infusion-related-reaction PT was reported in the posted AE table (Infusion organ rows therefore omitted rather than recorded as 0; pyrexia 12.5%, chills 7.5%, flushing 5.0% occurred but were not labeled infusion reactions). Toxicity_rows are all-cause (pooled N=40) from CT.gov posted results; G3+ rows use serious AEs as a proxy.