Lifastuzumab vedotin

Discontinued

DNIB0600A; DNIB-0600A; RG7599; RG-7599; RO5541081; RO-5541081; LIFA; anti-NaPi2b ADC; NaPi2b-ADC

Target

NaPi2b (sodium-dependent phosphate transport protein 2B) · SLC34A2

Sponsor

Genentech/Roche

Indication

NaPi2b+ epithelial ovarian cancer (platinum-sensitive recurrent in Ph1b; also platinum-resistant ovarian & NSCLC in Ph Ia)

Target family

SLC transporter

RP2D dose

2.4 mg/kg

Q3W (Ph1b: + carboplatin AUC6 cycles 1-6 ± bevacizumab 15 mg/kg)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

2 adverse-event terms

Ocular

Any-grade

20%

G3+

10%

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

20%

Express.

Retina / RPE

Express.

Dominant tissue

Lens

Surface subtype

Visual

Reversibility

Unknown

Reported ocular events

Vision blurred20%

G3+ 0%

Cataract12%

G3+ 10%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

3.5

DAR

Payload

MMAE

Tubulin inhibitor (anti-microtubule)

Linker structureC28H40N6O7

[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H])c([H])c1[H]

Payload structureC39H67N5O7

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

Lifastuzumab

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None (conventional IgG1 Fc; no effector-silencing mutations reported)

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

MC-vc-PAB (vedotin); ADCdb: Mc-Val-Cit-PABC

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys (random cysteine; maleimide)

Symmetry

Symmetric

DAR (mean)

3.5

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor (anti-microtubule)

Released catabolite

Unconjugated MMAE

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

ADCdb reports clinical objective response rate 34.00% (ITT) in platinum-resistant ovarian cancer (Phase 2); preclinical tumor growth inhibition ~19.6-62.8% across PDX models, correlating with higher SLC34A2 (NaPi2b) expression. Released payload MMAE is a potent tubulin-polymeriza

Dosing & regimen

Dosing

RP2D dose

2.4 mg/kg

Schedule

Q3W (Ph1b: + carboplatin AUC6 cycles 1-6 ± bevacizumab 15 mg/kg)

Route

Fractionated

n at RP2D

41 (Ph1b combination, OAE cohort; Ph Ia single-agent RP2D n=63; randomized Ph2 LIFA arm n=47)

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

20 %

OAE grade 3+

10 %

OAE data status

reported

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

20 %

Dominant tissue

Lens

Surface subtype

Visual

Grading scale

CTCAE (unversioned)

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: Symptom-driven reportingScale: CTCAE (unversioned)Denominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

lifastuzumab-vedotin

Approval status

Discontinued

Approval year

UniProt

O95436

ADCdb ADC

DRG0UQTJG

ADCdb antibody

ANI0MRPNB

ADCdb target

TAR0AABNG

Primary source

Gynecol Oncol 2020;158(3):631-639 (Phase 1b LIFA + carboplatin AUC6 ± bevacizumab in platinum-sensitive recurrent ovarian cancer, N=41; PMID 32534811); ocular AE rates via The Oncologist 2024 ADC ocular-AE review (academic.oup.com/oncolo/article/29/11/e1435); single-agent Clin Cancer Res 2020;26(2):364-372 (PMID 31540980); randomized Ph2 vs PLD Ann Oncol 2019 (S0923-7534(19)45469-0); ADCdb DRG0UQTJG / linker LIN0SQEDQ

Aliases & development codes

DNIB0600A; DNIB-0600A; RG7599; RG-7599; RO5541081; RO-5541081; LIFA; anti-NaPi2b ADC; NaPi2b-ADC

Notes

MMAE (vedotin) anti-NaPi2b ADC; Genentech/Roche; development discontinued (randomized Ph2 vs pegylated liposomal doxorubicin improved ORR but did NOT significantly improve PFS: HR 0.78, P=0.34; 95 randomized [47 LIFA/48 PLD], Ann Oncol 2019). The QUALIFYING ocular AE data (blurred vision 20% [no G3+]; cataract 12% [G3+ 10%]) come from the Phase 1b LIFA + carboplatin ± bevacizumab combination cohort (N=41); attribution to LIFA is confounded by carboplatin and by the older, heavily pretreated PSOC population (cataract is unusual for an MMAE ADC and atypical of the corneal/conjunctival ocular-surface pattern seen with MMAF ADCs). Ocular %s were obtained from The Oncologist 2024 ADC ocular-AE review citing the primary Gynecol Oncol 2020 paper; the primary abstract (PubMed) did not separately list ocular AEs. CLEAN single-agent toxicity is from Phase Ia (Clin Cancer Res 2020, PMID 31540980): treatment-related G3+ at RP2D (n=63) = neutropenia 10%, anemia 3%, pneumonia 3%; any-grade (pooled N=87, regardless of attribution) = fatigue 59%, nausea 49%, decreased appetite 37%, vomiting 32%, peripheral sensory neuropathy 29%. Combination Phase 1b G3+ hematologic (neutropenia 54% [22/41], thrombocytopenia 32% [13/41], anemia 7% [3/41]) is carboplatin-driven. Pulmonary toxicities 34% (14/41) in the combination, incl. 1 G2 pneumonitis leading to discontinuation; NaPi2b is expressed in lung (potential on-target). RP2D 2.4 mg/kg Q3W IV across all phases. Antibody = humanized IgG1 anti-NaPi2b (confirmed Ann Oncol 2019); conventional random interchain-Cys conjugation; DAR ADCdb 3-4 (vedotin platform mean ~3.5); linker Mc-Val-Cit-PABC (LIN0SQEDQ, identical to other vedotins). CTCAE version not stated in accessed abstracts (trials ~2013-2018; era-typical v4.0). No hepatic or infusion-reaction data retrievable. Synonyms: DNIB0600A, RG7599, RO5541081, LIFA.