← Atlas
Brentuximab vedotin FDA-approved Adcetris; SGN-35
Sponsor
Seagen (now Pfizer)
Target family
TNF receptor superfamily
RP2D dose
1.8 mg/kg (max 180 mg) Q3W RP2D
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
5%
Hepatic
31%
Neutrop.
54%
Thrombo.
28%
Anemia
33%
GI
42%
ILD
25%
Neuro.
52%
Also reported Other · 1320 · 18 systems
37 adverse-event terms
Ocular Toxicity Target expression Compare
sagittal schematic · Reversible
↳ Tissues shaded by reported adverse-event rate.
Reported ocular events
Lacrimation increased 6.85%
Eye disorders - Other, specify 5.13%
Retinol binding protein increased 2.56%
Necrotising retinitis 0.91%
Hallucination, visual 0.58%
Conjunctival hyperaemia 0.4%
Conjunctivitis bacterial 0.4%
Uveitis (anterior/intermediate) — also blurred vision, dry eye, conjunctivitis as rare PTs -
Per-trial detail
Adverse events by trial Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma · PHASE2 — 434 events, n=251 A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lympho · PHASE3 — 264 events, n=662 ECHELON-2 · PHASE3 — 186 events, n=223 Nivolumab & Brentuximab Vedotin Consolidation After Autologous SCT in Patients W · PHASE2 — 186 events, n=59 A Study of Brentuximab Vedotin Combined With Nivolumab for Relapsed or Refractor · PHASE1|PHASE2 — 170 events, n=91 Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refracto · PHASE2 — 166 events, n=39 Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy i · PHASE3 — 162 events, n=476 Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV · PHASE1|PHASE2 — 157 events, n=20 A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Pe · PHASE2 — 147 events, n=27 Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young · PHASE3 — 125 events, n=295 CheckMate 812 · PHASE3 — 120 events, n=22 Brentuximab Vedotin and Chemotherapy in CD30+ PMBL, Diffuse Large B-Cell, and Gr · PHASE1|PHASE2 — 116 events, n=31 A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma · PHASE2 — 114 events, n=172 Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies · PHASE2 — 113 events, n=83 Study of Brentuximab Vedotin Combined With RCHOP or RCHP in Front-line Treatment · PHASE2 — 112 events, n=73 Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients · PHASE2 — 111 events, n=57 A Brentuximab Vedotin Trial for Patients Who Have Previously Participated in a B · PHASE2 — 110 events, n=110 A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgk · PHASE4 — 105 events, n=60 C25007 (R/R cHL or sALCL) · Phase 4 — 104 events, n=60 COBRA · PHASE2 — 101 events, n=150 Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 · PHASE2 — 101 events, n=13 Brentuximab Vedotin in Chinese Participants With Relapsed/Refractory CD30-Positi · PHASE2 — 100 events, n=39 A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Resi · PHASE3 — 92 events, n=167 Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Di · NA — 89 events, n=41 ALCANZA · PHASE3 — 87 events, n=66 A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less · PHASE2 — 84 events, n=82 Study of Brentuximab Vedotin Combined With Bendamustine in Patients With Hodgkin · PHASE1|PHASE2 — 83 events, n=55 Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30- · PHASE2 — 81 events, n=48 CheckMate 436 · PHASE1|PHASE2 — 80 events, n=144 Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patie · PHASE2 — 79 events, n=68 Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With · PHASE2 — 79 events, n=48 Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage · PHASE1|PHASE2 — 79 events, n=41 Brentuximab Vedotin (Recombinant) for IV Infusion - Special Drug Use Surveillanc — 78 events, n=284 SGN+Benda · PHASE1|PHASE2 — 78 events, n=65 C25006 (CD30+ nonlymphomatous malignancies) · Phase 2 — 70 events, n=46 C25006 (CD30+ nonlymphomatous malignancies) · Phase 2 — 70 events, n=28 C25006 (CD30+ nonlymphomatous malignancies) · Phase 2 — 70 events, n=9 SG035-0006 (BV retreatment) · Phase 2 — 68 events, n=78 A Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin · PHASE2 — 63 events, n=52 BV-ICE · PHASE1|PHASE2 — 62 events, n=45 A Study of Brentuximab Vedotin Treatment in Chinese Adults With CD30-Positive Cu · PHASE4 — 52 events, n=10 CheckMate 744 · PHASE2 — 51 events, n=72 Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or · PHASE1|PHASE2 — 50 events, n=36 Dose Ranging Study of Brentuximab Vedotin in Adults With Lupus · PHASE2 — 50 events, n=16 Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemi · PHASE4 — 49 events, n=50 Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma · PHASE2 — 46 events, n=34 A Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Ped · PHASE1|PHASE2 — 45 events, n=59 Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed · PHASE2 — 45 events, n=28 A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplast · PHASE2 — 42 events, n=58 BRAVOS · PHASE1|PHASE2 — 42 events, n=26 Brentuximab Vedotin and Lenalidomide in Treating Patients With Stage IB-IVB Rela · PHASE2 — 41 events, n=26 SGN35-012 (R/R NHL) · Phase 2 — 40 events, n=103 Special Drug Use Surveillance for Brentuximab Vedotin Intravenous Infusion "Rela — 39 events, n=94 Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients W · PHASE1|PHASE2 — 36 events, n=45 A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 · PHASE2 — 35 events, n=23 A Study of Retreatment With Brentuximab Vedotin in Subjects With Classic Hodgkin · PHASE2 — 34 events, n=11 A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma · PHASE2 — 33 events, n=102 Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodg · PHASE2 — 33 events, n=46 Pivotal relapsed cHL (Study 1) · Phase 2 — 31 events, n=102 Pivotal relapsed sALCL (Study 2) · Phase 2 — 30 events, n=58 Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides With Variable CD · PHASE2 — 30 events, n=36 A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Syst · PHASE1 — 29 events, n=20 BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma · PHASE2 — 28 events, n=16 ECHELON-2 (Study 6) · Phase 3 — 27 events, n=223 Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy · PHASE2 — 27 events, n=77 AETHERA (Study 3) · Phase 3 — 23 events, n=167 ECHELON-3 (Study 8) · Phase 3 — 23 events, n=112 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors · PHASE2 — 23 events, n=18 Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma · PHASE2 — 22 events, n=34 Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or · PHASE2 — 21 events, n=10 ECHELON-1 (Study 5) · Phase 3 — 20 events, n=662 ALCANZA (Study 4) · Phase 3 — 20 events, n=66 Japan Special Drug-Use Surveillance (PTCL) · post-marketing (RWD) — 20 events, n=31 AHOD1331 (Study 7) · Phase 3 — 18 events, n=296 Brentuximab Vedotin (SGN-35) in Transplant Eligible Patients With Relapsed or Re · PHASE2 — 15 events, n=65 ECHELON-3 (Study 8) · Approved — 14 events, n=112 BV in MF/CTCL · Phase 2 — 14 events, n=36 Study 1 (relapsed cHL) · Approved — 13 events, n=102 Bretuximab · PHASE2 — 13 events, n=25 C25002 (China R/R cHL/sALCL) · Phase 2 — 8 events, n=284 SG035-0003 (Study 1, relapsed classical Hodgkin lymphoma post-auto-HSCT) · Approved — 8 events, n=102 FIL_SGN01 · PHASE2 — 8 events, n=15 Unattributed cohort — 7 events, n=296 SG035-0004 (Study 2, relapsed systemic anaplastic large cell lymphoma) · Approved — 7 events, n=58 Unattributed cohort — 5 events, n=662 ECHELON-2 (Study 6) · Approved — 5 events, n=223 ECHELON-1 (Study 5) · Approved — 3 events, n=662 ECHELON-1 (Study 5, previously untreated Stage III/IV cHL; BV + AVD) · Approved — 3 events, n=662 AETHERA (Study 3) · Approved — 3 events, n=167 Studies 1-4 (pooled monotherapy) · Approved — 2 events, n=393 AHOD1331 (Study 7) · Approved — 2 events, n=296 Japan Drug-Use Surveillance (untreated HL) · post-marketing (RWD) — 2 events, n=112 Drug Use Surveillance for Brentuximab Vedotin Intravenous Infusion "Untreated CD — 2 events, n=112 Study 2 (relapsed sALCL) · Approved — 2 events, n=58 Unattributed cohort — 1 event, n=662 Unattributed cohort — 1 event, n=223 ALCANZA (Study 4) · Approved — 1 event, n=66 Unattributed cohort — 1 event Unattributed cohort — 1 event Unattributed cohort — 1 event Unattributed cohort — 1 event Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma PHASE2 real-world n=251 CTCAE NR (ClinicalTrials.gov C
434 adverse-event terms · 22 systems · expand a system below
Constipation
43.43% non-serious
Diarrhoea
30.68% non-serious
Vomiting
19.92% non-serious
Stomatitis
16.33% non-serious
Abdominal pain
12.35% non-serious
Gastrooesophageal reflux disease
10.76% non-serious
Dyspepsia
9.16% non-serious
Dry mouth
4.78% non-serious
Haemorrhoids
3.19% non-serious
Abdominal distension
2.79% non-serious
Oral pain
2.79% non-serious
Abdominal pain upper
1.99% non-serious
Abdominal discomfort
1.59% non-serious
Dysphagia
1.59% non-serious
Flatulence
1.59% non-serious
Haematochezia
1.2% non-serious
Gingival pain
1.2% non-serious
Aphthous ulcer
0.8% non-serious
Eructation
0.8% non-serious
Gingival bleeding
0.8% non-serious
Haemorrhoidal haemorrhage
0.8% non-serious
Hypoaesthesia oral
0.8% non-serious
Salivary hypersecretion
0.8% non-serious
Mouth haemorrhage
0.4% serious
Abdominal tenderness
0.4% non-serious
Anal haemorrhage
0.4% non-serious
Anal incontinence
0.4% non-serious
Dental caries
0.4% non-serious
Gastric haemorrhage
0.4% non-serious
Intussusception
0.4% non-serious
Lip oedema
0.4% non-serious
Lip swelling
0.4% non-serious
Noninfective sialoadenitis
0.4% non-serious
Odynophagia
0.4% non-serious
Oesophageal dilatation
0.4% non-serious
Oesophageal haemorrhage
0.4% non-serious
Oesophageal spasm
0.4% non-serious
Oral disorder
0.4% non-serious
Oral dysaesthesia
0.4% non-serious
Pancreatitis acute
0.4% non-serious
Paraesthesia oral
0.4% non-serious
Periodontal disease
0.4% non-serious
Rectal haemorrhage
0.4% non-serious
Vision blurred
6.77% non-serious
Lacrimation increased
2.79% non-serious
Photophobia
0.8% non-serious
Visual impairment
0.8% non-serious
Conjunctival hyperaemia
0.4% non-serious
Epiretinal membrane
0.4% non-serious
Eye pruritus
0.4% non-serious
Vitreous detachment
0.4% non-serious
Xerophthalmia
0.4% non-serious
Conjunctivitis
0.4% non-serious
Conjunctivitis bacterial
0.4% non-serious
02 Construct
Molecular anatomy Linker structure C28H40N6O7
[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] copy
Payload structure C39H67N5O7
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 copy
03 Antibody
Antibody & Fc engineering Antibody
cAC10 (brentuximab)
Fc modifications
None inferred
Glycoengineering
Standard inferred
Effector silencing
None inferred
C1q binding
Retained inferred
Epitope / domain
Membrane-proximal CD30 extracellular epitope, residues aa 163-178
Linker
MC-vc-PAB (vedotin)
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
DAR homogeneity
Heterogeneous
Cleavage trigger
Cathepsin B (Val-Cit)
Release control
Conditional
Hydrophilicity mask
None inferred
Platform
Seagen 'vedotin' platform
Conjugation site
Interchain cysteines liberated by partial reduction of the 4 inter-chain disulfides unver.
In-vitro stability
98%@10d/human-plasma
Stability note
acAb t½ 4–6 days; <2% free MMAE at 10 d in human plasma in vitro; 2–6%/day conjugate loss in cyno via retro-Michael (Alley 2008, Lyon 2014)
Mechanism
Tubulin inhibitor
Released catabolite
MMAE (monomethyl auristatin E)
Mechanistic subtype
Tubulin-auristatin
Plasma protein binding (%)
68 % unver.
Hydrophobicity · logD₇.₄
hydrophilic −2 +2.7 +4 lipophilic
Bioactivity note
ADCdb reports MMAE payload potency with IC50 as low as 1.9 pM in CD30+ Karpas-299 cells (range across cell lines up to ~3300 ng/mL). Mechanism: MMAE binds tubulin and disrupts microtubules, causing G2/M arrest and apoptosis after antigen-mediated internalization and Val-Cit linke
RP2D dose
1.8 mg/kg (max 180 mg)
07 Pharmacology
Clinical pharmacokinetics By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews
Intact ADC Total antibody Free payload Cmax 18.89 (27% CV) ug/mL +4
24.7 (26% CV) ug/mL +4
2.72 (272% CV) ng/mL +4
AUC 46.14 (62% CV) day*ug/mL +4
112.0 (27% CV) day*ug/mL +4
20.29 (212% CV) day*ng/mL +4
Tmax near end of infusion (qualitative) +5
0.13 (0.08, 0.24) day +4
approximately 1-3 (after end of infusion) day +5
t½ approximately 4-6 day +5
— approximately 3-4 day +5
CL 1.96 (105% CV) L/day +4
— — Vd approximately 6-10 L +5
— —
hover a value for dose / population / source · “+N” marks additional reported values
08 Ocular & expression
Ocular profile & eye-tissue target expression Target profile → Target expression in eye tissues (HCA detection · HPA bulk)
Cross-trial comparability · source-verified
Ascertainment: Symptom-driven reporting Scale: Mixed Denominator: RP2D ⚠ Not comparable: symptom-driven ascertainment + mixed grading scale
Dose & schedule → ocular toxicity · ocular AE (any-grade) by cohort
n=60 · C25007 (R/R cHL or sALCL)
n=78 · SG035-0006 (BV retreatment)
n=31 · Brentuximab Vedotin and Chemotherapy in CD30+ PMBL, Diffuse Large B-Cell, and Gr
n=13 · Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30
n=27 · A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Pe
n=73 · Study of Brentuximab Vedotin Combined With RCHOP or RCHP in Front-line Treatment
n=251 · Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
n=91 · A Study of Brentuximab Vedotin Combined With Nivolumab for Relapsed or Refractor
n=39 · Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refracto
n=476 · Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy i
n=20 · Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV
n=41 · Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Di
n=59 · Nivolumab & Brentuximab Vedotin Consolidation After Autologous SCT in Patients W
n=39 · Brentuximab Vedotin in Chinese Participants With Relapsed/Refractory CD30-Positi
n=110 · A Brentuximab Vedotin Trial for Patients Who Have Previously Participated in a B
n=57 · Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients
n=60 · A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgk
n=295 · Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young
n=68 · Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patie
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 09 Identity & registry
Identifiers, registry & notes ADC id
brentuximab-vedotin
Approval status
FDA-approved
Primary source
ADCETRIS DailyMed label; imputed from >=10% reporting threshold
Aliases & development codes
Adcetris; SGN-35
Notes
5% imputed (label has no Eye disorders SOC at >=10% threshold)