Free base; DXd is a single (1S,9S) exatecan-derivative stereoisomer (no payload salt counter-ion)
Bystander
Yes
PAMPA rank
-
MW
493.5 Da
XLogP3
0
logD₇.₄
1.4
TPSA
129 Ų
pKa
9.2 pKa
Charge pH 7.4
+1
H-bond donors
3
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C26H24FN3O6
PubChem CID
117888634
ADCdb payload
PAY0UXDSB
Potency IC50 (nM)
0.31
Hydrophobicity · logD₇.₄
hydrophilic −2+1.4+4 lipophilic
Bioactivity note
Payload DXd is a topoisomerase I (TOP1/DNA topoisomerase 1) inhibitor; ADCdb lists DNA topoisomerase 1 as the payload's therapeutic target. No numeric payload IC50 reported on the ADCdb page. Clinical/efficacy notes from ADCdb: ~39% objective response rate in Phase 1 NSCLC; xenog
n=3 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
4.8 mg/kg
Q3W IV
6.7%
n=15 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
4.8 mg/kg
Q3W IV
6.1%
n=33 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
5.6 mg/kg
Q3W IV
15%
n=60 · U3-1402 metastatic breast (Daiichi 2020)
5.6 mg/kg
Q3W IV
5%
n=40 · U3-1402 metastatic breast (Daiichi 2020)
5.6 mg/kg
Q3W
2.7%
· HERTHENA-Lung01
6.4 mg/kg
Q3W IV
13.3%
n=15 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
3.2/4.8/6.4 mg/kg (uptitration)
Q3W IV
8.3%
n=12 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
4.2/6.4 mg/kg (uptitration)
Q3W IV
8.3%
n=12 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
3.2->4.8->6.4 mg/kg (uptitration)
Q3W IV
8%
n=50 · HERTHENA-Lung01
up-titration (3.2 then 4.8 then 6.4 mg/kg)
Q3W
8%
· HERTHENA-Lung01
6.4 mg/kg
Q3W IV
3.2%
n=31 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
8.0 mg/kg
Q3W IV
16.7%
n=6 · U3-1402 HER3+ metastatic breast (U31402-A-J101)
Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.
HER3 (ERBB3)-targeted DXd ADC on the deruxtecan platform: fully human IgG1 patritumab, DAR 8, cleavable MC-GGFG linker (ADCdb LIN0ECMCR, shared with trastuzumab deruxtecan / datopotamab deruxtecan / trastuzumab rezetecan), conventional interchain-Cys conjugation, DXd (exatecan-derivative TopoI inhibitor) payload. RP2D = 5.6 mg/kg Q3W (HERTHENA-Lung01, NCT04619004, Phase 2, n=225, CTCAE v5.0).
OCULAR PROFILE IS MILD (the reason this ADC qualifies): vision blurred is the ONLY eye-disorder preferred term in the CT.gov posted results -- 2.7% (6/225) at 5.6 mg/kg and 8.0% (4/50) in the up-titration arm; all non-serious, no serious eye disorders in either arm, and no eye disorder appears among grade>=3 TEAEs (so oae_g3plus_pct=0). No corneal/keratitis/dry-eye PTs were reported (below the 5% CT.gov reporting threshold). Subtype = Visual. dose_oae_available=TRUE (two dose contexts). Markedly milder than the sibling TROP2 deruxtecan ADC datopotamab deruxtecan (~36% ocular AEs / corneal-dominant in the DB).
Dominant non-ocular toxicities: hematologic (thrombocytopenia 43.6% any / 20.9% G3+; neutropenia ~37.3% any / 19.1% G3+; anaemia 32.9% any / 14% G3+) and the deruxtecan-platform AESI interstitial lung disease (centrally adjudicated drug-related 5.3%, including one grade-5 death; updated ESMO 2024 analysis 6.2%). GI is high any-grade but low-grade (nausea 65.3%). Hepatic transaminase elevations modest (AST 16.9%, ALT 11.6%).
Sourcing/derivation notes: any-grade grouped neutropenia (37.3% = 84/225) derived by summing the two CT.gov posted-results PTs (neutropenia 23 + neutrophil count decreased 61); the same additive grouping reproduces the published thrombocytopenia 43.6% exactly (33+65=98/225), validating the method. G3+ heme and ILD from the primary JCO 2023 publication (= ASCO Post coverage); updated values (ESMO 2024, ESMO Open S2059-7029(24)00358-2) differ slightly with longer follow-up (anaemia G3+ 15.1%, ILD 6.2%) and are noted per-row. Infusion-related reactions and peripheral neuropathy were NOT in the CT.gov otherEvents list (i.e., <5%); left blank, not 0. Payload physchem are DB-standard DXd values (consistent with T-DXd/Dato-DXd rows; xLogP3 0.0 per DB convention). Linker physchem confirmed directly from the ADCdb LIN0ECMCR page.
Regulatory: NOT FDA-approved -- BLA received a Complete Response Letter (June 2024) citing inspection findings at a third-party manufacturer (per Merck/Daiichi Sankyo); the phase 3 HERTHENA-Lung02 (NCT05338970) subsequently did not improve overall survival. No FDA label exists, hence Tier A unavailable; overall Tier B from the primary publication + registered CT.gov results. Sponsor: Daiichi Sankyo with Merck (MSD) co-development (Merck code MK-1022).