ADC TOXICITY ATLAS
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Upifitamab rilsodotin

Discontinued
UpRi; XMT-1536; XMT 1536; XMT1536
Sponsor
Mersana Therapeutics
Indication
Platinum-resistant ovarian cancer (NaPi2b+ high-grade serous ovarian/fallopian tube/peritoneal)
Target family
SLC transporter
RP2D dose
36 mg/m2 (capped at ~80 mg flat)
Q4W (every 4 weeks / every 28 days)RP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
2 adverse-event terms

Ocular

Any-grade
41%
G3+
9%
RP2D
sagittal schematic · Unknown

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
-
Limbus
AE
-
Express.
-
Conjunctiva
AE
-
Express.
-
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Reversibility
Unknown
Reported ocular events
Vision blurred41%
G3+ 6%n=97
Keratopathy-
G3+ 9%n=97
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
~12 (range 10-15 AF-HPA per mAb; ADCdb states 10-12)
DAR
Payload
Tubulin inhibitor (microtubule)
Linker structure
structure not applicable
Payload structureC43H74N6O8
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCCCO)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
03
Antibody

Antibody & Fc engineering

Antibody
XMT-1535
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Dolaflexin (Fleximer/PHF polyacetal polymer; mal-(BA-EG2)-AF-HPA-Ala)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Random cysteine (maleimide thioether); Dolaflexin/Fleximer polymer scaffold (3-5 polymers per mAb)
Symmetry
Symmetric
DAR (mean)
~12 (range 10-15 AF-HPA per mAb; ADCdb states 10-12)
DAR homogeneity
Heterogeneous
Plasma t½
-
Cleavage trigger
Intracellular proteolysis (amide/protease-cleavable AF-HPA-Ala released from Fleximer/PHF polymer)
Release control
Conditional
Hydrophilicity mask
Hydrophilic-linker
Formula
-
Linker MW
-
Linker TPSA
-
Linker xLogP
-
ADCdb linker
LIN0SWMHT
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
Auristatin F-HPA (AF-HPA)
Class
Auristatin
Mechanism
Tubulin inhibitor (microtubule)
Released catabolite
Auristatin F-HPA (AF-HPA); intratumorally metabolized to auristatin F (AF)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
803.1 Da
XLogP3
4.3
logD₇.₄
-
TPSA
170 Ų
pKa
9 pKa
Charge pH 7.4
+1
H-bond donors
4
H-bond acceptors
9
IC50 (HCEC)
-
Formula
C43H74N6O8
PubChem CID
71135741
ADCdb payload
PAY0SIHVM
Bioactivity note
ADCdb (DRG0OZSZX) reports in vitro EC50 0.52 nM in OVCAR-3 (NaPi2b+ ovarian) cells; clinical ORR 34% overall and 35% in SLC34A2/NaPi2b-high tumors. Payload AF-HPA is a tubulin/microtubule-targeting auristatin (target mechanism listed as Microtubule).
06
Dosing & regimen

Dosing

RP2D dose
36 mg/m2 (capped at ~80 mg flat)
Schedule
Q4W (every 4 weeks / every 28 days)
Route
IV
Fractionated
No
n at RP2D
97
Dose basis
BSA
Trial phase
Phase 1
Dose-OAE available
No
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
41 %
OAE grade 3+
9 %
OAE data status
reported
Severity (weighted)
18.6
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
41 %
Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Grading scale
-
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
upifitamab-rilsodotin
Approval status
Discontinued
Approval year
-
UniProt
O95436
ADCdb ADC
DRG0OZSZX
ADCdb antibody
ANI0TYNXL
ADCdb target
TAR0AABNG
Primary source
SGO 2022 / Gynecol Oncol 2022;166(Suppl 1) abstract 076 (UpRi Phase 1 expansion, ovarian, n=97); ADCdb DRG0OZSZX
Aliases & development codes
UpRi; XMT-1536; XMT 1536; XMT1536
Notes
OCULAR (priority, the reason this ADC qualifies): from SGO 2022 conference abstract (Gynecol Oncol 2022;166 Suppl 1, abstr 076), pooled Phase 1b expansion n=97 across 36-43 mg/m2 + 80 mg flat cap, Q4W IV. Blurred vision 41% any / 6% G3+; keratopathy 9% G3+ (any-grade keratopathy NOT reported -> ae_corneal_pct left blank). oae_any_pct=41 (max any-grade PT = blurred vision); oae_g3plus_pct=9 (max G3+ PT = keratopathy). Dominant tissue corneal/visual; auristatin-F (MMAF-like, but AF-HPA) off-target ocular-surface toxicity, NOT on-target (NaPi2b not corneal-expressed). Reversibility not explicitly stated for UpRi (class effect typically reversible) -> Unknown. Grading scale not stated in abstract (likely CTCAE v5.0) -> left blank. NON-OCULAR: most common TRAEs were fatigue, nausea, transient AST increase, thrombocytopenia, decreased appetite; most common G3+ were transient AST increase, fatigue, anemia, thrombocytopenia. EXACT percentages for hepatic (AST), hematologic (thrombocytopenia/anemia/neutropenia), and GI (nausea) are behind paywalled abstract/journal sources (ScienceDirect/Elsevier, ResearchGate, OncLive/TargetedOnc all returned 403) and are therefore left BLANK per the convention (blank != 0). Dose reductions 28% and discontinuations 10% due to TRAEs (n=97). Peripheral neuropathy not prominent (AF-HPA designed for low PN); no PN rate retrieved -> blank. Pneumonitis ~9.6% included as a D-tier Pulmonary row (denominator uncertain). COMPOSITION/CHEMISTRY: anti-NaPi2b (SLC34A2) humanized IgG1-kappa antibody XMT-1535; Dolaflexin platform = hydrophilic Fleximer/PHF polyacetal polymer (3-5 polymers per mAb) carrying ~10-15 AF-HPA, attached by random-cysteine maleimide thioether (cleavable). DAR: ADCdb 10-12, ADC Review 12-15, preclinical 10-15 -> reported ~12 (10-15). Payload AF-HPA = auristatin F hydroxypropylamide (PubChem CID 71135741; C43H74N6O8, MW 803.1, XLogP 4.3, TPSA 170); controlled bystander, metabolized intratumorally to auristatin F (AF). Charge +1 = physiological protonation of the basic amine (C-terminus masked as hydroxypropylamide -> neutral, membrane-permeable, unlike charged MMAF; PubChem formal charge 0). LINKER PHYSCHEM: ADCdb linker LIN0SWMHT is a POLYMER linker (Dolaflexin/Fleximer) with no discrete SMILES/formula/MW/TPSA/xLogP (not chemically defined for a single small molecule) -> linker_smiles/formula/mw/tpsa/xlogp left blank. PROGRAM STATUS: discontinued 2023. UPLIFT (NCT03319628 registrational cohort) missed primary endpoint (investigator ORR 15.6%, 22/141 NaPi2b+); UP-NEXT Phase 3 maintenance (NCT05329545) terminated Sep 2023. DERIVED columns intentionally NOT filled (computed downstream): severity, FcgammaR/C1q status, dna_damage subtype, stability conditional/unconditional, HCA/HPA expression.