Rovalpituzumab tesirine

Discontinued

Rova-T; SC16LD6.5; SC-0002; SC0001-SCX; P256HB60FF; DrugBank DB13017

Target

Delta-like protein 3 (DLL3) · DLL3

Sponsor

AbbVie (originally Stemcentrx)

Indication

DLL3+ small cell lung cancer (SCLC)

Target family

Notch ligand

RP2D dose

0.3 mg/kg

Q6W x2 cyclesRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

11 adverse-event terms

Ocular

Any-grade

0.54%

G3+

1.4%

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Periorbital/adnexa

Surface subtype

Mixed

Reversibility

Unknown

Reported ocular events

Vision blurred8.3%

n=12

Dry eye8.3%

n=12

Cataract8.3%

n=12

Retinopathy8.3%

n=12

Periorbital oedema6.7%

n=30

Periorbital swelling0.54%

n=368

Angle-closure glaucoma0.27%

n=368

Eyelid oedema0.27%

n=368

Cytomegalovirus chorioretinitis-

G3+ 0.27%

Eye disorders (any preferred term)0%

n=287

Photophobia-

G3+ 1.4%n=74

Per-trial detail

Adverse events by trial

Rova-T in DLL3+ advanced solid tumors (NCT02709889)Phase 1/20.4 mg/kg Q6W (6-week cycle)n=12CTCAE 4.03 (CTCAE grading vePooledC

CT.gov NCT02709889 Other(non-serious) AE >=5% (any-grade non-serious proxy; subgroups pooled by dose) NCT02709889 0.4 mg/kg

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

Neurologic (other)26

Ataxia

0/12

Aphasia

0/12

Asterixis

0/12

Brain oedema

0/12

Cerebral haematoma

0/12

Disturbance in attention

0/12

Dizziness

0/12

Dizziness postural

0/12

Dysaesthesia

0/12

Dysgeusia

0/12

Encephalopathy

0/12

Head discomfort

0/12

Hemiparesis

0/12

Hydrocephalus

0/12

Hypersomnia

0/12

Hypoaesthesia

0/12

Lethargy

0/12

Mental impairment

0/12

Metabolic encephalopathy

0/12

Migraine

0/12

Neuropathy peripheral

0/12

Paraesthesia

0/12

Peripheral sensory neuropathy

0/12

Somnolence

0/12

Spinal cord compression

0/12

Syncope

0/12

GI24

Dermatologic21

General20

Pulmonary19

Infections18

Metabolic17

Musculoskeletal17

Renal13

Ocular12

Conjunctival haemorrhage

0/12

Diplopia

0/12

Eye irritation

0/12

Eye pain

0/12

Eye pruritus

0/12

Eye swelling

0/12

Ocular discomfort

0/12

Orbital oedema

0/12

Photophobia

0/12

Uveitis

0/12

Vision blurred

0/12

Visual impairment

0/12

Other12

Psychiatric11

Investigations10

Cardiac7

Hematologic6

Injury6

Vascular6

Neoplasms4

Ear2

Endocrine1

Hepatic1

Immune1

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

SG3199 (PBD dimer)

DNA cross-linker

Linker structureC41H65N5O15

[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])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])C(=O)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])[H])c([H])c1[H]

Payload structureC33H36N4O6

CC1=CN2[C@@H](C1)C=NC3=CC(=C(C=C3C2=O)OC)OCCCCCOC4=C(C=C5C(=C4)N=C[C@@H]6CC(=CN6C5=O)C)OC

Antibody

Antibody & Fc engineering

Antibody

Rovalpituzumab (SC16)

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

0.2

Dev code

SC16.56

Epitope / domain

DLL3 N-terminal DSL/EGF region

Linker & conjugation

Linker chemistry

Linker profile

Linker

Mal-PEG8-Val-Ala-PABC (tesirine; SG3249)

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys (maleimide; random cysteines)

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Cathepsin B (Val-Ala)

Release control

Conditional

Hydrophilicity mask

Discrete-PEG-spacer

Formula

C41H65N5O15

Linker MW

867.991 Da

Linker TPSA

247.85 Å²

Linker xLogP

-0.2829

ADCdb linker

LIN0YRUBS

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

SG3199 (PBD dimer)

Class

PBD dimer

Mechanism

DNA cross-linker

Released catabolite

SG3199 (pyrrolobenzodiazepine [PBD] dimer)

Mechanistic subtype

DNA-crosslinker-PBD

Stereochem / salt

(11aS,11a'S)-configured PBD dimer (single defined stereoisomer); free base (no salt)

Bystander

Partial

PAMPA rank

584.7 Da

XLogP3

2.8

logD₇.₄

2.5

TPSA

102 Å²

pKa

5 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

0.1515 nM

Formula

C33H36N4O6

PubChem CID

90132565

ADCdb payload

PAY0LZRXU

Potency IC50 (nM)

151.5

CAS no.

1595275-71-0

Hydrophobicity · logD₇.₄

hydrophilic −2+2.5+4 lipophilic

Bioactivity note

SG3199 (free warhead) is a potent DNA minor-groove interstrand cross-linking PBD dimer with mean GI50 ~151.5 pM across a panel of human solid-tumor and hematological cell lines (Hartley et al., Sci Rep 2018). ADCdb reports clinical/efficacy data for the ADC: Phase 2 SCLC ORR 12.4

Dosing & regimen

Dosing

RP2D dose

0.3 mg/kg

Schedule

Q6W x2 cycles

Route

Fractionated

n at RP2D

339

Dose basis

TBW

Trial phase

Phase 2

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0.54 %

OAE grade 3+

1.4 %

OAE data status

reported

Severity (weighted)

1.14

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Periorbital/adnexa

Surface subtype

Mixed

Grading scale

CTCAE v4.0

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 v4Denominator: RP2D

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

0.05 mg/kg

Q3W

33.33%

n=3 · First-in-human Rova-T (Rudin 2017)

0.05 mg/kg

Q3W

n=3 · First-in-human Rova-T (Rudin 2017)

0.1 mg/kg

Q3W

n=1 · First-in-human Rova-T (Rudin 2017)

0.2 mg/kg

Q3W

9.09%

n=11 · First-in-human Rova-T (Rudin 2017)

0.2 mg/kg

Q6W (6-week cycle)

4.65%

n=43 · Rova-T in DLL3+ advanced solid tumors

0.2 mg/kg

Q6W (6-week cycle)

2.33%

n=43 · Rova-T in DLL3+ advanced solid tumors

0.2 mg/kg

Q6W (6-week cycle)

n=43 · Rova-T in DLL3+ advanced solid tumors

0.2 mg/kg

Q3W

n=11 · First-in-human Rova-T (Rudin 2017)

0.3 mg/kg

Q6W x2

8.3%

n=12 · NCT03026166 (Rova-T + nivolumab + ipilimumab)

0.3 mg/kg

Q6W x2

6.7%

n=30 · NCT03026166 (Rova-T + nivolumab)

Rova-T 0.3 mg/kg

Rova-T Q6W (Day1 C1&C3) x2 + nivolumab/ipilimumab

6.67%

n=30 · Rova-T + nivolumab +/- ipilimumab (SCLC)

0.3 mg/kg

Q6W (6-week cycle)

3.45%

n=145 · Rova-T in DLL3+ advanced solid tumors

Rova-T 0.3 mg/kg

Rova-T Q6W (Day1 C1&C3) x2 + nivolumab/ipilimumab

3.33%

n=30 · Rova-T + nivolumab +/- ipilimumab (SCLC)

0.3 mg/kg

Q6W (6-week cycle)

2.76%

n=145 · Rova-T in DLL3+ advanced solid tumors

0.3 mg/kg

Q6W (6-week cycle)

2.07%

n=145 · Rova-T in DLL3+ advanced solid tumors

0.3 mg/kg

Q6W (6-week cycle)

1.38%

n=145 · Rova-T in DLL3+ advanced solid tumors

0.3 mg/kg

Q6W (6-week cycle)

0.69%

n=145 · Rova-T in DLL3+ advanced solid tumors

0.3 mg/kg

Q6W omitting every 3rd cycle

0.54%

n=368 · MERU

0.3 mg/kg

Q6W x2

0.54%

n=372 · MERU

0.3 mg/kg

Q6W omitting every 3rd cycle

0.27%

n=368 · MERU

0.3 mg/kg

0.27%

0.3 mg/kg

Q6W (6-week cycle)

n=145 · Rova-T in DLL3+ advanced solid tumors

0.3 mg/kg

Q6W omitting every 3rd cycle

n=368 · MERU

0.3 mg/kg

Q6W

n=7 · First-in-human Rova-T (Rudin 2017)

Rova-T 0.3 mg/kg

Rova-T Q6W (Day1 C1&C3) x2 + nivolumab/ipilimumab

n=30 · Rova-T + nivolumab +/- ipilimumab (SCLC)

0.3 mg/kg

Q6W x2

n=287 · TAHOE

0.4 mg/kg

Q3W

33.33%

n=3 · First-in-human Rova-T (Rudin 2017)

0.4 mg/kg

Q6W (6-week cycle)

8.33%

n=12 · Rova-T in DLL3+ advanced solid tumors

0.4 mg/kg

Q6W (6-week cycle)

n=12 · Rova-T in DLL3+ advanced solid tumors

0.4 mg/kg

Q3W

n=3 · First-in-human Rova-T (Rudin 2017)

0.8 mg/kg

Q3W

n=2 · First-in-human Rova-T (Rudin 2017)

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

rovalpituzumab-tesirine

Approval status

Discontinued

Approval year

UniProt

Q9NYJ7

ADCdb ADC

DRG0ULCEQ

ADCdb antibody

ANI0NBQGD

ADCdb target

TAR0HELFC

Primary source

Morgensztern TRINITY Clin Cancer Res 2019 (PMID 31506387); Blackhall TAHOE & Johnson MERU JTO 2021 (PMIDs 34537440/33823285); Rudin Lancet Oncol 2017 (PMID 27932068); ADCdb DRG0ULCEQ

Aliases & development codes

Rova-T; SC16LD6.5; SC-0002; SC0001-SCX; P256HB60FF; DrugBank DB13017

Notes

DLL3-targeted PBD-dimer ADC (SC16 humanized IgG1 + tesirine [SG3249] Val-Ala/PEG8 maleimide linker + SG3199 PBD dimer payload, DAR 2). Sponsor AbbVie (originally Stemcentrx, acquired 2016). Never approved; orphan-drug designation only; entire program discontinued 2019 after the Phase 3 TAHOE (2L) and MERU (maintenance) trials failed for efficacy/futility. ADCdb lists DRG0ULCEQ; aliases include Rova-T, SC16LD6.5, SC-0002. NOTE a DISTINCT program "SC-002" (ADCdb DRG0UUEEH; Mansfield Lung Cancer 2020) exists and should not be conflated with Rova-T. DOMINANT (non-ocular) TOXICITIES = serosal-effusion/capillary-leak/edema syndrome + photosensitivity, NOT classic ADC ocular toxicity: pleural effusion TRINITY 32% (G3+ 5%)/MERU 26.6%/TAHOE ~28.6%; pericardial effusion TRINITY 15% (G3+ 4%)/MERU 16.8%/TAHOE ~19.9%; peripheral edema TRINITY 31% (G3+ 2%)/MERU 25.8%; photosensitivity reaction TRINITY 36% (G3+ 7%)/MERU 24.7%/TAHOE 16%; thrombocytopenia TRINITY 22% (G3+ 11%). These respiratory/serosal/dermatologic/edema PTs fall outside the schema's organ_system enum so are recorded here rather than as toxicity_rows. OCULAR (priority): monotherapy ocular toxicity is essentially absent at RP2D — TRINITY (n=339) reported 0 ocular AEs and TAHOE (n=287) reported 0 eye disorders in the MedDRA SOC; MERU (n=368) reported ONLY 3 serious eye AEs (periorbital swelling 2/368=0.54%, angle-closure glaucoma 1/368=0.27%, eyelid oedema 1/368=0.27%), most likely adnexal manifestations of the systemic edema syndrome rather than ocular-surface toxicity; Phase 1 (Rudin 2017) reported a single Grade 3 photophobia (1/74 SCLC). NO keratopathy/corneal or conjunctival signal in any monotherapy trial. The only meaningful ocular signal is in the COMBINATION trial NCT03026166 (Rova-T 0.3 mg/kg Q6W + nivolumab ± ipilimumab): vision blurred 3.3% (1/30 doublet) to 8.3% (1/12 triplet), and in the 12-patient triplet arm dry eye, cataract, retinopathy, xerophthalmia, eyelid oedema, periorbital oedema, ocular hyperaemia, eye pruritus and visual impairment each 8.3% (1/12) — all non-serious and heavily CONFOUNDED by checkpoint-inhibitor immune-related ocular AEs, so not cleanly attributable to Rova-T. ae_corneal/conjunctival/dry-eye/blurred-vision left blank for the ocular group because monotherapy reported none and sub-threshold (<5% non-serious) PTs are not tabulated. CTCAE v4.03 (confirmed Rudin 2017 & TRINITY). Linker physchem (LIN0YRUBS) identical to Loncastuximab tesirine (shared tesirine linker); SG3199 payload physchem are standard shared PBD-dimer values. No peripheral neuropathy reported (expected for a DNA-crosslinker PBD payload).