Farletuzumab (naked Ab)

Discontinued

MORAb-003

Target

Folate receptor alpha · FOLR1

Sponsor

Morphotek/Eisai

Indication

FOLR1+ ovarian

Target family

GPI-anchored

RP2D dose

2.5 mg/kg

Q1WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

3 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.02%

Limbus

Express.

0.07%

Conjunctiva

Express.

0.19%

Lens

Express.

Retina / RPE

Express.

3.21%

0.4 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Reversible

Reported ocular events

Lacrimation increased5.3%

Ocular adverse event (keratopathy / dry eye / blurred vision)0%

n=367

Retinal detachment (serious)-

G3+ 0%

Per-trial detail

Adverse events by trial

NCT01218516 (Phase 2, lung adenocarcinoma)Phase 2Farletuzumab 7.5 mg/kg IV (load C1W1+C1W2) + platinum doublet (carbo/paclitaxel, carbo/pemetrexed, or cisplatin/pemetrexed) q3w x4-6 cycles (combination phase)n=64CTCAE NRCto verify

CT.gov NCT01218516 all-cause mortality (derived G5; includes non-AE/PD deaths) NCT01218516

333 adverse-event terms · 22 systems · expand a system below

Infections38

Urinary tract infection

6.2%

4/64

Pneumonia

4.7%G3+ 0%

3/64

Upper respiratory tract infection

4.7%G3+ 0%

3/64

Bronchitis

3.1%

2/64

Candidiasis

3.1%

2/64

Catheter site infection

1.6%G3+ 1.6%

1/64

Herpes dermatitis

1.6%

1/64

Abdominal Sepsis

1.6%

1/64

Catheter site cellulitis

1.6%

1/64

Nasopharyngitis

1.6%

1/64

Oral candidiasis

1.6%

1/64

Otitis media

1.6%

1/64

Pharyngitis

1.6%

1/64

Skin infection

1.6%

1/64

Cellulitis

0/64

Clostridial infection

0/64

Conjunctivitis infective

0/64

Cystitis

0/64

Encephalitic Infection

0/64

Fungal infection

0/64

Gastroenteritis

0/64

Lower respiratory tract infection

0/64

Onychomycosis

0/64

Pneumonia streptococcal

0/64

Respiratory tract infection

0/64

Respiratory tract infection fungal

0/64

Septic shock

0/64

Tooth abscess

0/64

Furuncle

0/64

Influenza

0/64

Liver abscess

0%G3+ 0%

0/64

Rhinitis

0/64

Tonsillitis

0/64

Herpes zoster

0/64

Lymph gland infection

0/64

Respiratory syncytial virus infection

0/64

Empyema

0%G3+ 0%

0/64

Encephalitic infection

—G3+ 0%

Neurologic (other)34

Pulmonary33

General29

GI28

Metabolic20

Musculoskeletal20

Dermatologic19

Vascular15

Hematologic11

Ocular11

Conjunctivitis

4.7%

3/64

Eye irritation

3.1%

2/64

Visual acuity reduced

3.1%

2/64

Dry eye

1.6%

1/64

Eye pruritus

1.6%

1/64

Lacrimation increased

1.6%

1/64

Photopsia

1.6%

1/64

Visual impairment

1.6%

1/64

Diplopia

0%G3+ 0%

0/64

Vision blurred

0/64

Eyelid ptosis

0/64

Injury11

Renal11

Investigations10

Neoplasms10

Psychiatric9

Cardiac7

Ear6

Other5

Hepatic4

Overall/Summary1

Immune1

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

DAR

Payload

N/A (naked antibody)

Linker structure

structure not applicable

Payload structure

structure not applicable

Antibody

Antibody & Fc engineering

Antibody

farletuzumab

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

Linker & conjugation

Linker chemistry

Linker profile

Linker

N/A (naked antibody)

Class

Cleavage

Attachment

Conjugation

Not applicable (naked antibody)

Symmetry

N/A

DAR (mean)

DAR homogeneity

N/A

Plasma t½

Cleavage trigger

N/A

Release control

N/A

Hydrophilicity mask

N/A

Cell line

CHO-K1

Formula

Linker MW

Linker TPSA

Linker xLogP

ADCdb linker

In-vitro stability

N/A

Stability note

Naked anti-FOLR1 antibody — no payload, no linker. Plasma t½ governed by neonatal Fc receptor recycling typical of IgG1 (~21 d) but t½ axis is not toxicity-relevant for this molecule because there is no warhead

Payload

Payload & physicochemistry

Payload profile

Payload

N/A (naked antibody)

Class

Mechanism

Released catabolite

N/A

Mechanistic subtype

N/A

Stereochem / salt

N/A

Bystander

PAMPA rank

XLogP3

logD₇.₄

TPSA

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

PubChem CID

ADCdb payload

CAS no.

896723-44-7

Bioactivity note

Mechanism is payload-independent: farletuzumab is a naked anti-FRalpha mAb acting via ADCC, CDC, induction of autophagy, and inhibition of FRalpha-Lyn kinase growth signaling; it does not block folate binding/transport. No cytotoxic-payload IC50 applies.

Dosing & regimen

Dosing

RP2D dose

2.5 mg/kg

Schedule

Q1W

Route

Fractionated

n at RP2D

367

Dose basis

TBW

Trial phase

Phase 3

Dose-OAE available

Tox summary basis

RP2D

ADA rate (%)

0 %

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0 %

OAE grade 3+

0 %

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

None

Grading scale

CTCAE v3.0

Reversibility

Reversible

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

0.02 %

Cornea (limbal)

0.07 %

Conjunctiva

0.19 %

RPE

3.21 %

Retina (HPA)

0.4 nTPM

Cross-trial comparability

Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ Not comparable: symptom-driven ascertainment + grading scale not documented

Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort

Farletuzumab 1.25 mg/kg IV weekly + taxane (paclitaxel 175 or docetaxel 75) + carboplatin AUC5-6 q21d x6, then Far maintenance

IV weekly (chemo q21d x6)

5.3%

n=376 · Phase 3

1.25 mg/kg

5.3%

Farletuzumab 2.5 mg/kg IV weekly + paclitaxel 80 mg/m2 IV weekly

IV weekly (wk1-12 Cycle1, then 3-of-4-wk cycles)

n=279 · NCT00738699 (Phase 2, platinum-resistant/refractory ovarian)

Farletuzumab 2.5 mg/kg IV weekly + taxane (paclitaxel 175 or docetaxel 75) + carboplatin AUC5-6 q21d x6, then Far maintenance

IV weekly (chemo q21d x6)

2.8%

n=363 · Phase 3

2.5 mg/kg weekly

Weekly maintenance after 6 cycles carboplatin/taxane

n=367 · MORAb-003-004 (Vergote Phase 3, platinum-sensitive ovarian, first relapse)

Farletuzumab 7.5 mg/kg IV (load C1W1+C1W2) + platinum doublet (carbo/paclitaxel, carbo/pemetrexed, or cisplatin/pemetrexed)

q3w x4-6 cycles (combination phase)

4.7%

n=64 · NCT01218516 (Phase 2, lung adenocarcinoma)

Farletuzumab 7.5 mg/kg IV monotherapy (maintenance)

q3w until progression (monotherapy phase)

3.2%

n=31 · NCT01218516 (Phase 2, lung adenocarcinoma)

Farletuzumab 10 mg/kg load x2 wk then 5 mg/kg IV weekly + carboplatin AUC5 + paclitaxel 175 q3w OR PLD 30 q4w

IV weekly (chemo q3w or q4w)

n=141 · NCT02289950 (Phase 2, low-CA125 platinum-sensitive ovarian)

Farletuzumab 62.5 mg/m2 IV weekly (continued dose from parent MORAb-003-002)

IV weekly (up to ~37.7 months)

n=2 · NCT01018563 (open-label extension of NCT00318370)

Farletuzumab 100 mg/m2 IV weekly (continued dose from parent MORAb-003-002)

IV weekly (up to ~37.7 months)

100%

n=1 · NCT01018563 (open-label extension of NCT00318370)

Farletuzumab 100 mg/m2 IV weekly (+ paclitaxel 175 or docetaxel 75 + carboplatin AUC5-6 q21d during chemo period)

IV weekly (chemo D1 q21d)

7.4%

n=54 · MORAb-003-002

—

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.

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

Identity & registry

Identifiers, registry & notes

ADC id

farletuzumab

Approval status

Discontinued

Approval year

UniProt

P15328

ADCdb ADC

ADCdb antibody

ANI0TZBRZ

ADCdb target

TAR0QHAVI

Primary source

Vergote JCO 2016;34(19):2271 (PMID 27001568)

Aliases & development codes

MORAb-003

Notes

Naked antibody — 0% OAE confirms OAE signal is entirely payload-driven. V3.1: n=1100 is Vergote 2016 total Phase 3 enrollment across 3 farletuzumab arms; 2.5 mg/kg arm ~367.