Indatuximab ravtansine

Discontinued

BT-062; BT062; nBT-062; nBT062-DM4

Target

Syndecan-1 (CD138) · SDC1

Sponsor

Biotest (Biotest Pharma GmbH / Biotest AG)

Indication

Relapsed/refractory multiple myeloma

Target family

Other

RP2D dose

160 mg/m2

Q3WPooled

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

5 adverse-event terms

Ocular

Any-grade

6.3%

G3+

Pooled

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

3.1%

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Unknown

Reported ocular events

Any ocular adverse event (composite)6.3%

n=2

Corneal epithelial damage-

n=1

Corneal crystalline inclusions (corneal deposits)-

n=1

Dry eye-

n=1

Blurred vision-

n=1

Per-trial detail

Adverse events by trial

Phase 1/2a multi-dose monotherapy (NCT01001442) - Jagannath 2019Phase 1/240-160 mg/m2 (pooled; MTD/RP2D 140 mg/m2) IV on days 1, 8, 15 of each 28-day cyclen=35PooledB

CT.gov NCT01001442 posted results, adverseEventsModule otherEvents (MedDRA 17.1; all-cause, any grade, >=5% threshold) [11/35] NCT01001442 (CT.gov posted results); also PMID 30930134 (Jagannath, Clin Lymphoma Myeloma Leuk 2019)

67 adverse-event terms · 14 systems · expand a system below

Investigations12

ASPARTATE AMINOTRANSFERASE INCREASED

25.7%

9/35

ALANINE AMINOTRANSFERASE INCREASED

17.1%

6/35

BLOOD LACTATE DEHYDROGENASE INCREASED

11.4%

4/35

GAMMA-GLUTAMYLTRANSFERASE INCREASED

11.4%

4/35

OCCULT BLOOD POSITIVE

11.4%

4/35

AMYLASE INCREASED

8.6%

3/35

LYMPHOCYTE COUNT DECREASED

8.6%

3/35

BLOOD CREATINE PHOSPHOKINASE INCREASED

5.7%

2/35

BLOOD CREATININE INCREASED

5.7%

2/35

BLOOD URIC ACID INCREASED

5.7%

2/35

LIPASE INCREASED

5.7%

2/35

NEUTROPHIL COUNT DECREASED

5.7%

2/35

Musculoskeletal8

GI7

General6

Metabolic6

Dermatologic6

Hematologic5

Pulmonary5

Injury3

Neurologic (other)3

Infections2

Psychiatric2

Renal1

Vascular1

Construct

Molecular anatomy

Antibody

IgG4

Chimeric

Linker

Cleavable

3.5

DAR

Payload

DM4

Tubulin inhibitor

Linker structureC13H14N2O4S2

[H]c1nc(SSC([H])([H])C([H])([H])C([H])([H])C(=O)ON2C(=O)C([H])([H])C([H])([H])C2=O)c([H])c([H])c1[H]

Payload structureC39H56ClN3O10S

C/C/1=C\C=C\[C@H]([C@]2(C[C@@H](C([C@H]3[C@@](O3)([C@H](CC(=O)N(C4=C(C(=CC(=C4)C1)OC)Cl)C)OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)C)(C)C)OC(=O)N2)O)OC

Antibody

Antibody & Fc engineering

Antibody

Indatuximab (nBT062)

Isotype

IgG4

Origin

Chimeric

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None (native IgG4 backbone confers low effector function; no engineered silencing mutations)

FcγR binding

Weak/low

C1q binding

Weak/low

Epitope / domain

Linear epitope at CD138

Linker & conjugation

Linker chemistry

Linker profile

Linker

SPDB

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (SPDB)

Symmetry

Symmetric

DAR (mean)

3.5

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C13H14N2O4S2

Linker MW

326.399 Da

Linker TPSA

76.57 Å²

Linker xLogP

2.2093

ADCdb linker

LIN0VZYER

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

DM4

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (S-Me-DM4); primary lysosomal catabolite lysine-Nepsilon-SPDB-DM4

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Bystander

Yes

PAMPA rank

780.4 Da

XLogP3

3.2

logD₇.₄

TPSA

157 Å²

pKa

10.3 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H56ClN3O10S

PubChem CID

46926355

ADCdb payload

PAY0GTSVM

Potency IC50 (nM)

Hydrophobicity · logD₇.₄

hydrophilic −2+3+4 lipophilic

Bioactivity note

ADCdb DRG0AWUIJ reports tumor growth inhibition (TGI) measurements ranging 0-100% across multiple cell-line and PDX models, and clinical objective response rates of 3.20% and 5.90% depending on dosing regimen. No discrete payload IC50 listed on the ADCdb page. DM4 is a tubulin-bi

Dosing & regimen

Dosing

RP2D dose

160 mg/m2

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

all-doses pooled

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

6.3 %

OAE grade 3+

OAE data status

reported

Severity (weighted)

Keratopathy

3.1 %

Conjunctival

Dry eye

3.1 %

Blurred vision

3.1 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

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

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

100 mg/m²

IV on days 1, 8, 15 of each 28-day cycle

25%

n=4 · Phase 1/2a multi-dose monotherapy

40-160 mg/m2 (pooled; MTD/RP2D 140 mg/m2)

IV on days 1, 8, 15 of each 28-day cycle

2.9%

n=35 · Phase 1/2a multi-dose monotherapy

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

indatuximab-ravtansine

Approval status

Discontinued

Approval year

UniProt

P18827

ADCdb ADC

DRG0AWUIJ

ADCdb antibody

ANI0OXDFY

ADCdb target

TAR0SERWS

Primary source

Kelly et al. Clin Lymphoma Myeloma Leuk 2019;19(6):372-380 (PMID 30930134) [monotherapy/ocular]; Eaton et al. ADC ocular-AE review 2015 (PMC4677113) [ocular]; Kelly et al. Lancet Haematol 2021 (NCT01638936) [combination]

Aliases & development codes

BT-062; BT062; nBT-062; nBT062-DM4

Notes

BT-062: chimeric (hinge-unmodified) human IgG4 anti-CD138/syndecan-1 antibody (nBT062, chimerized from murine B-B4) conjugated to maytansinoid DM4 via SPDB disulfide linker at random lysines; DAR 3-4 per ADCdb (3.5 used as midpoint). Program (Biotest): two monotherapy Ph1 studies pooled in Kelly CLML 2019 (n=67 total: single-dose q3w NCT00723359 n=32, MTD 160 mg/m2; multi-dose D1,8,15 q4w n=35, MTD/RP2D 140 mg/m2) PLUS Ph1/2a combination NCT01638936 (n=64; indatuximab ravtansine + low-dose dexamethasone + lenalidomide [MTD 100 mg/m2] or pomalidomide [RP2D 100 mg/m2], D1,8,15 q4w). Program terminated. OCULAR (reason for inclusion): NO aggregate ocular rate was published. Eaton 2015 (PMC4677113) and Kelly CLML 2019 describe 2 distinct patients, both at 160 mg/m2 (single-dose schedule NCT00723359): (A) a male patient with corneal epithelial damage + crystalline corneal inclusions, grade 2, 3 days after cycle 3; (B) a female patient with dry eye + blurred vision, grade 2, 4 days after cycle 4. Both events were grade 2 and 'medically significant'; reversibility/follow-up were explicitly NOT reported (per Eaton 2015). Off-target corneal toxicity typical of DM4 maytansinoids (CD138/syndecan-1 is not expressed on cornea; SPDB-DM4 class, cf. mirvetuximab/anetumab/tusamitamab/coltuximab). The ocular percentages (oae_any 6.3%, ae_corneal/dry_eye/blurred_vision 3.1% each) are DERIVED lower bounds (2 distinct pts and 1 pt per PT, against the single-dose study population N=32); the source states only counts, not rates, and the 160 mg/m2 cohort-specific rate is HIGHER because not all 32 received 160 mg/m2 (the 160 cohort N was not separately reported). oae_g3plus_pct left blank: no G3+ ocular AE was reported (both documented events were G2), but these were spontaneously-reported AEs (no prospective ophthalmologic exam of all patients), so a true 0% G3+ is not established. CTCAE version not specified in accessible sources. HEMATOLOGIC toxicity_rows are from the COMBINATION study (N=64, Lancet Haematol 2021) and are CONFOUNDED by the lenalidomide/pomalidomide + dexamethasone backbone (IMiD-driven cytopenias); NOT clean single-agent attribution -> tagged line_context >=2L (not RP2D) and excluded from the monotherapy RP2D summary slice. Monotherapy safety: 88% of AEs were grade 1-2, most common diarrhea + fatigue (no percentages published in accessible sources -> GI/Hepatic/Pulmonary/Neurologic-PN/Infusion summary rows omitted rather than fabricated). Combo ORR: +lenalidomide 71.7% (33/46), +pomalidomide 70.6% (12/17). CHEMISTRY: linker LIN0VZYER (SPDB) physchem (SMILES/formula/MW 326.399/TPSA 76.57/xLogP 2.2093) identical to the existing SPDB-DM4 DB rows. DM4 payload physchem = DB-standard maytansinoid values (tier C). linker_plasma_t_half not measured for indatuximab specifically (SPDB-DM4 class ~5.5-7 d) -> left blank. Released catabolite and cleavage mechanism are class-inferred (SPDB disulfide reductively cleaved -> DM4 / S-methyl-DM4). IgG4 isotype chosen for low effector function (Ikeda CCR 2009). Cross-ref IDs: DrugBank DB16195; PubChem SID 472423471/223370377/160671957.