ADC TOXICITY ATLAS
← Atlas

SC-002 (rovalpituzumab, DLL3, PBD/SG3199)

Discontinued
SC-002; SC 002; SC002; Stemcentrx SC-002
Sponsor
Stemcentrx, Inc. / AbbVie, Inc.
Indication
Relapsed/refractory small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC)
Target family
Notch ligand
RP2D dose
0.4 mg/kg
Every 9 weeks (Q9W) [declared MTD]; dose-escalation was Q3WRP2D
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
2.9%
G3+
0%
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
Visual
Surface subtype
Visual
Reversibility
Unknown
Reported ocular events
Photophobia2.9%
Any eye disorder (grade >=3)-
G3+ 0%
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
2
DAR
Payload
DNA minor-groove interstrand crosslinker (DNA-damaging agent)
Linker structure
structure not applicable
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
03
Antibody

Antibody & Fc engineering

Antibody
Rovalpituzumab (engineered with 2 site-specific cysteine residues)
Isotype
IgG1
Origin
Humanized
Fc modifications
-
Glycoengineering
-
Effector silencing
Not reported; IgG1 carries 2 engineered cysteines for site-specific conjugation (conjugation handle, not Fc-silencing mutations)
FcγR binding
Retained
C1q binding
Unknown
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Plasma-stable valine-alanine (Val-Ala) dipeptide linker (site-specific; distinct from Rova-T tesirine/SG3249)
Class
Peptide
Cleavage
Cleavable
Attachment
Site-specific (engineered Cys)
Conjugation
Site-specific conjugation via 2 introduced cysteine residues (homogeneous)
Symmetry
Site-specific (paired)
DAR (mean)
2
DAR homogeneity
Homogeneous
Plasma t½
-
Cleavage trigger
Cathepsin B (lysosomal cysteine protease); Val-Ala dipeptide
Release control
Conditional
Hydrophilicity mask
None
Formula
-
Linker MW
-
Linker TPSA
-
Linker xLogP
-
ADCdb linker
-
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
SC-DR002 (PBD dimer warhead); ADCdb payload = SG3199 (PAY0LZRXU)
Class
PBD dimer
Mechanism
DNA minor-groove interstrand crosslinker (DNA-damaging agent)
Released catabolite
SC-DR002 PBD dimer warhead (SG3199-class pyrrolobenzodiazepine dimer)
Mechanistic subtype
DNA-crosslinker-PBD
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
584.7 Da
XLogP3
2.8
logD₇.₄
-
TPSA
102 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
0
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C33H36N4O6
PubChem CID
90132565
ADCdb payload
PAY0LZRXU
Bioactivity note
ADCdb (DRG0UUEEH) reports clinical efficacy for SC-002 Phase 1 (terminated; relapsed/refractory SCLC and large-cell neuroendocrine carcinoma): overall ORR 14.29% (5/35 partial responses); in DLL3-positive patients 2/17 (11.8%) partial response. No payload IC50 / ADC binding affin
06
Dosing & regimen

Dosing

RP2D dose
0.4 mg/kg
Schedule
Every 9 weeks (Q9W) [declared MTD]; dose-escalation was Q3W
Route
IV
Fractionated
No
n at RP2D
8
Dose basis
TBW
Trial phase
Phase 1
Dose-OAE available
Yes
Tox summary basis
-
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
2.9 %
OAE grade 3+
0 %
OAE data status
reported
Severity (weighted)
0.87
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
Visual
Surface subtype
Visual
Grading scale
CTCAE v4
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability
Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
sc-002
Approval status
Discontinued
Approval year
-
UniProt
Q9NYJ7
ADCdb ADC
DRG0UUEEH
ADCdb antibody
ANI0NBQGD
ADCdb target
PATR0RIOXT
Primary source
Morgensztern 2020, Lung Cancer 145:126-131 (PMID 32438272)
Aliases & development codes
SC-002; SC 002; SC002; Stemcentrx SC-002
Notes
IDENTITY / DISAMBIGUATION (important): SC-002 is a DLL3-directed ADC (Stemcentrx -> AbbVie) that uses the SAME antibody (rovalpituzumab) and the SAME class of PBD-dimer warhead as Rova-T, but a DISTINCT linker/conjugation: a plasma-stable Val-Ala dipeptide linker with SITE-SPECIFIC conjugation via 2 introduced cysteine residues giving a homogeneous DAR2 (~95% DAR2). Rova-T (rovalpituzumab tesirine, SC16LD6.5) uses tesirine/SG3249 with conventional conjugation. Do NOT merge SC-002 and Rova-T toxicity datasets despite shared antibody/payload and the 'rovalpituzumab' name. CITATION CORRECTION: the wave1_input attributed the source to 'Mansfield et al.' The actual first author is Morgensztern D (Morgensztern D, Johnson M, Rudin CM, Rossi M, Lazarov M, Brickman D, Fong A. 'SC-002 in patients with relapsed or refractory small cell lung cancer and large cell neuroendocrine carcinoma: Phase 1 study.' Lung Cancer 2020;145:126-131. PMID 32438272; PMCID PMC8173700; NCT02500914). OCULAR (qualifying signal): a SINGLE grade 2 photophobia in 1/35 patients (~2.9%), at 0.2 mg/kg Q3W (not the MTD), considered possibly treatment-related, reported only in the safety narrative (below Table 3 threshold). No corneal/conjunctival/dry-eye/blurred-vision events reported (left blank, not zero). No grade >=3 ocular AE. Reversibility not stated. CTCAE v4.03. Photophobia may be related to the prominent PBD photosensitivity phenomenon rather than ocular-surface toxicity, hence ocular_surface_subtype = Visual. This is a weak/low-magnitude OAE signal. SAFETY-POPULATION CAVEAT: the only safety table (Table 3) is the POOLED phase 1a/1b full analysis set (n=35, all dose levels 0.025-0.4 mg/kg). There is no separate RP2D-cohort safety table (MTD cohort = 8 pts at 0.4 mg/kg Q9W). All toxicity_rows therefore reflect the pooled n=35 population; line_context records this and flags the MTD/RP2D. Treat per-organ percentages as pooled-across-doses, not RP2D-specific. SIGNATURE TOXICITY: serosal effusions dominate (pleural 43%/20%, pericardial 26%/3%) with hypoalbuminemia (17%/6%) and peripheral edema (31%/3%) -> capillary-leak/serosal-effusion phenotype characteristic of PBD-dimer ADCs. Photosensitivity reaction 20%/3% (skin SOC; the grade 3 photosensitivity was the DLT/MTD-defining event at 0.4 mg/kg Q9W) - not captured as a toxicity_row because 'Skin' is not in the organ_system enum, but it is the headline cutaneous toxicity. Other notable AEs (not in organ enum): fatigue 31%/6%, pyrexia 23%, hypotension 17%, hyponatraemia 11%/9%, pulmonary embolism 6%/6%. Overall grade 3 in 21/35 (60%) and grade 4 in 2/35 (6%); SAEs in ~66%. NOT REPORTED (left blank per convention, NOT zero): neutropenia; peripheral neuropathy (consistent with a non-tubulin DNA-crosslinker payload); infusion-related reactions; AST/ALT/bilirubin elevations; vomiting; diarrhea. OUTCOME: development discontinued for systemic toxicity and limited efficacy (ORR 14.29% [PR only, no CR]). ADCdb CROSS-REFS (DRG0UUEEH): antibody ANI0NBQGD (Rovalpituzumab); antigen TAR0HELFC (DLL3); payload PAY0LZRXU (SG3199); ChEMBL CHEMBL3990011; TTD D0D4OL. ADCdb lists DAR=2, conjugate type 'Undisclosed', status Phase 1 (Terminated), sponsor Stemcentrx/AbbVie. ADCdb does NOT disclose a linker LIN id or linker physchem (SMILES/formula/MW/TPSA/xLogP) -> adcdb linker fields left blank. Linker is qualitatively 'plasma-stable'; no numeric half-life or stability % reported. PAYLOAD PHYSCHEM: standard SG3199 values from PubChem CID 90132565 applied per shared-payload convention (MW 584.7, formula C33H36N4O6, XLogP 2.8, TPSA 102). The actual named warhead is SC-DR002, an SG3199-class PBD dimer. logD7.4 and pKa not in the literature (blank); charge (neutral) and bystander (Yes) are tier-C inferences from PBD-dimer chemistry. DERIVED COLUMNS (DNA-damage subtype, stability conditional/unconditional, FcgammaR/C1q, severity scores, HCA/HPA expression) intentionally left for downstream computation.