Payload Information

General Information of This Payload
Payload ID
PAY0SIHVM
Name
Auristatin F hydroxypropylamide (AF-HPA)
Synonyms
Auristatin f-hpa; Auristatin F hydroxypropylamide; 7A55BK9DV3; XMT-1267; 1415659-09-4; UNII-7A55BK9DV3; SCHEMBL14315837; L-PHENYLALANINAMIDE, N,N-DIMETHYL-L-VALYL-L-VALYL-(3R,4S,5S)-3-METHOXY-5-METHYL-4-(METHYLAMINO)HEPTANOYL-(.ALPHA.R,.BETA.R,2S)-.BETA.-METHOXY-.ALPHA.-METHYL-2-PYRROLIDINEPROPANOYL-N-(3-HYDROXYPROPYL)-; L-Phenylalaninamide, N,N-dimethyl-L-valyl-L-valyl-(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(alphaR,betaR,2S)-beta-methoxy-alpha-methyl-2-pyrrolidinepropanoyl-N-(3-hydroxypropyl)-; N,N-DIMETHYL-L-VALYL-L-VALYL-(3R,4S,5S)-3-METHOXY-5-METHYL-4-(METHYLAMINO)HEPTANOYL-(.ALPHA.R,.BETA.R,2S)-.BETA.-METHOXY-.ALPHA.-METHYL-2-PYRROLIDINEPROPANOYL-N-(3-HYDROXYPROPYL)-L-PHENYLALANINAMIDE; N,N-Dimethyl-L-valyl-L-valyl-(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(alphaR,betaR,2S)-beta-methoxy-alpha-methyl-2-pyrrolidinepropanoyl-N-(3-hydroxypropyl)-L-phenylalaninamide
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Target(s) Microtubule (MT)
 Target Info 
Structure
Formula
C43H74N6O8
Isosmiles
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCCCO)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
PubChem CID
71135741
InChI
InChI=1S/C43H74N6O8/c1-13-29(6)38(48(10)43(55)36(27(2)3)46-42(54)37(28(4)5)47(8)9)34(56-11)26-35(51)49-23-17-21-33(49)39(57-12)30(7)40(52)45-32(41(53)44-22-18-24-50)25-31-19-15-14-16-20-31/h14-16,19-20,27-30,32-34,36-39,50H,13,17-18,21-26H2,1-12H3,(H,44,53)(H,45,52)(H,46,54)/t29-,30+,32-,33-,34+,36-,37-,38-,39+/m0/s1
InChIKey
XHXOHGJMQNOIIO-LMPBRMKVSA-N
IUPAC Name
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(2S)-1-(3-hydroxypropylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide
Pharmaceutical Properties
Molecule Weight
803.1
Polar area
170
Complexity
1260
xlogp Value
4.3
Heavy Count
57
Rot Bonds
24
Hbond acc
9
Hbond Donor
4
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Upifitamab rilsodotin [Phase 3]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
34.00% (all)
35.00% (SLC34A2 high)
29.00% (SLC34A2 low)
High SLC34A2 expression (SLC34A2+++; 66,000 SLC34A2 antigens/cell)
Patients Enrolled
Ovarian cancer patients with 1-3 prior lines in platinum-resistant; 4 prior lines patients regardless of platinum status.
Administration Dosage
36 or 43 mg/m 2 IV once every 4 weeks.
Related Clinical Trial
NCT Number NCT03319628  Phase Status Phase 1/2
Clinical Description
Open-label, dose escalation to reach mtd. the mtd will be confirmed in parallel cohorts: patients with platinum-resistant ovarian cancer; patients with non-squamous nsclc, adenocarcinoma subtype.
Experiment 2 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT05329545  Phase Status Phase 3
Clinical Description
A phase 3, randomized, double-blind, placebo-controlled, multicenter study of upifitamab rilsodotin (XMT-1536) as post-platinum maintenance therapy for participants with recurrent, platinum-sensitive, ovarian cancer (up-next).
Experiment 3 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Patients with a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, including fallopian tube, or primary peritoneal cancer and have received 1-3 prior lines of therapy.
Related Clinical Trial
NCT Number NCT04907968  Phase Status Phase 1
Clinical Description
Upifitamab rilsodotin (XMT-1536) an open-label, multicenter, dose escalation and expansion study of upifitamab rilsodotin in combination with carboplatin in participants with high grade serous ovarian cancer (UP GRADE-A).
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 58.60% (Day 35) Moderate SLC34A2 expression (SLC34A2++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Lung cancer PDX model (PDX: CTG-0178)
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 60.60% (Day 28) Moderate SLC34A2 expression (SLC34A2++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Lung cancer PDX model (PDX: CTG-0178)
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.40% (Day 17) Moderate SLC34A2 expression (SLC34A2++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Non-small cell lung cancer PDX model (PDX: CTG-0860)
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.10% (Day 28) High SLC34A2 expression (SLC34A2+++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Lung cancer PDX model (PDX: CTG-0852)
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.40% (Day 35) High SLC34A2 expression (SLC34A2+++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Lung cancer PDX model (PDX: CTG-0852)
Experiment 6 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.70% (Day 62) High SLC34A2 expression (SLC34A2+++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

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In Vivo Model Lung cancer PDX model (PDX: CTG-0852)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.00% (Day 28) High SLC34A2 expression (SLC34A2+++)
Method Description
Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm3. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg.

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In Vivo Model Ovarian adenocarcinoma CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.52 nM
Method Description
OVCAR3 cells were grown in RPMI1640 media supplemented with 20% FBS and 1% penicillin/streptomycin,seeded at a density of 5, 000 cells per well in 100 L of growth media in a 96-well,white flat-bottom plate. Following overnight incubation,the media was replaced with 100 L of fresh media containing the test compounds at a 3-fold titration up to 33 nmol/L. The treated cells were incubated for 96 hours at 37°C in the presence of 5% CO2. In the OVCAR3 cell line,XMT-1536 was cytotoxic in a 96-hour cellular cytotoxicity assay.

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In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
XMT-1592 [Phase 1/2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Related Clinical Trial
NCT Number NCT04396340  Phase Status Phase 1/2
Clinical Description
A phase 1b, first-in-human, dose escalation and expansion study of XMT-1592 in patients with solid tumors likely to express NAPI2B.
ASN-004 [Phase 1]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 17 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 28.20% (Day 21) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 0.3 mg/kg single dose.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 54.30% (Day 60) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 0.3 mg/kg Q4D 4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 55.50% (Day 12) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 1 mg/kg Q4D 4.
In Vivo Model Cervical advanced-stage cancer CDX model
In Vitro Model Cervical advanced-stage cancer Cervical advanced-stage cancer cells Homo sapiens
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.20% (Day 21) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 1 mg/kg single dose.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.30% (Day 21) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg single dose.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Negative 5T4 expression (5T4-)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. A tumor xenograft model derived from the NCI-N87 human gastric tumor cell line [5T4-; 4, 400 binding sites per cell] and high expression of HER2. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg single dose.

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In Vivo Model Gastric cancer CDX model
In Vitro Model Gastric cancer Gastric cancer cells Homo sapiens
Experiment 7 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Negative 5T4 expression (5T4-)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. A tumor xenograft model derived from the NCI-N87 human gastric tumor cell line [5T4-; 4, 400 binding sites per cell] and high expression of HER2. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg Q4D 3.

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In Vivo Model Gastric cancer CDX model
In Vitro Model Gastric cancer Gastric cancer cells Homo sapiens
Experiment 8 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 60) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 1 mg/kg Q4D 4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 9 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 60) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg Q4D 4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 10 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 1 mg/kg Q4D 4.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 11 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg Q4D 4.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 12 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 6mg/kg Q4D 4.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 13 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was studied in a tumor xenograft model derived from the A431 (human cervical epidermoid,5T4+; 88, 000 binding sites per cell) tumor cell line. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 10 mg/kg single dose.

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In Vivo Model Cervical cancer CDX model
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 14 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 70) High 5T4 expression (5T4+++)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 1 mg/kg Q4D 4.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells (5T4 overexpression) CVCL_0062
Experiment 15 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 70) High 5T4 expression (5T4+++)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 3 mg/kg Q4D 4.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells (5T4 overexpression) CVCL_0062
Experiment 16 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 70) High 5T4 expression (5T4+++)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 6mg/kg Q4D 4.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells (5T4 overexpression) CVCL_0062
Experiment 17 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 70) High 5T4 expression (5T4+++)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ubcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of ASN004 was 10 mg/kg single dose.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells (5T4 overexpression) CVCL_0062
Revealed Based on the Cell Line Data
Click To Hide/Show 32 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.07 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.09 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.09 nM
High 5T4 expression (5T4+++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder squamous cell carcinoma SCaBER cells CVCL_3599
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma 5637 cells CVCL_0126
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
High 5T4 expression (5T4+++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Amelanotic melanoma A-375 cells CVCL_0132
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.15 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
Experiment 7 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.17 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 8 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.18 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Endocervical adenocarcinoma HeLa cells CVCL_0030
Experiment 9 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.23 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 10 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 11 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.26 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 12 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.31 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma SW780 cells CVCL_1728
Experiment 13 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.34 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Glioblastoma U-87MG cells CVCL_0022
Experiment 14 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.42 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 15 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.42 nM
High 5T4 expression (5T4+++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells (5T4 overexpression) CVCL_0062
Experiment 16 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.44 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Gestational choriocarcinoma JEG-3 cells CVCL_0363
Experiment 17 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.56 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 18 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.57 nM
Negative 5T4 expression (5T4-)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 19 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.62 nM
Negative 5T4 expression (5T4-)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 20 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.66 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma TCCSUP cells CVCL_1738
Experiment 21 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.76 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Recurrent bladder carcinoma HT-1197 cells CVCL_1291
Experiment 22 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.78 nM
Negative 5T4 expression (5T4-)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma RT-4 cells CVCL_0036
Experiment 23 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.93 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma T24 cells CVCL_0554
Experiment 24 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.95 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Experiment 25 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.03 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Breast ductal carcinoma HCC1937 cells CVCL_0290
Experiment 26 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.05 nM
Low 5T4 expression (5T4+)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Lung large cell carcinoma NCI-H1299 cells CVCL_0060
Experiment 27 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.06 nM
High 5T4 expression (5T4+++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma HT-1376 cells CVCL_1292
Experiment 28 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.34 nM
Negative 5T4 expression (5T4-)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Lung small cell carcinoma DMS 114 cells CVCL_1174
Experiment 29 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.53 nM
Negative 5T4 expression (5T4-)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma UM-UC-3 cells CVCL_1783
Experiment 30 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.28 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Bladder carcinoma J82 cells CVCL_0359
Experiment 31 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
9.01 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Hepatoblastoma Hep-G2 cells CVCL_0027
Experiment 32 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
9.03 nM
Moderate 5T4 expression (5T4++)
Method Description
The cytotoxic effect of ASN004 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing bladder,breast,cervical,colon,gastric,glioblastoma,liver,lung,melanoma,placenta,and prostate cancers.
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
XMT-1522 [Terminated in phase 1]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 49) Positive HER2 expression (HER2+++/++)
Method Description
XMT-1522 (3 mg/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of JIMT-1 cells with HER2 expression with high expression.
In Vivo Model JIMT-1 CDX model
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
References
Ref 1 Safety and efficacy of XMT-1536 in ovarian cancer: A subgroup analysis from the phase I expansion study of XMT-1536, a NaPi2b antibody-drug conjugate. Ann. Oncol. 2020 Sept; 31(4):Supplement S627-S628.
Ref 2 A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Upifitamab Rilsodotin (XMT-1536) as Post-Platinum Maintenance Therapy for Participants With Recurrent, Platinum-Sensitive, Ovarian Cancer (UP-NEXT), NCT05329545
Ref 3 Upifitamab Rilsodotin (Xmt-1536) An Open-Label, Multicenter, Dose Escalation And Expansion Study Of Upifitamab Rilsodotin In Combination With Carboplatin In Participants With High Grade Serous Ovarian Cancer (Upgrade-A), NCT04907968
Ref 4 The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b. Mol Cancer Ther. 2021 May;20(5):896-905.
Ref 5 A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1592 In Patients With Solid Tumors Likely to Express NaPi2b, NCT04396340
Ref 6 ASN004, A 5T4-targeting scFv-Fc Antibody-Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models. Mol Cancer Ther. 2021 Aug;20(8):1327-1337.
Ref 7 A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab Emtansine. Mol Cancer Ther. 2019 Oct;18(10):1721-1730. doi: 10.1158/1535-7163.MCT-19-0207. Epub 2019 Jul 10.

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