Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0OZSZX
ADC Name
Upifitamab rilsodotin
Synonyms
XMT 1536; XMT-1536; XMT1536; UpRi
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Organization
Mersana Therapeutics, Inc.
Drug Status
Phase 3
Indication
In total 5 Indication(s)
Ovarian cancer [ICD11:2C73]
Phase 3
Lung cancer [ICD11:2C25]
Phase 2
Non-small cell lung cancer [ICD11:2C25]
Phase 2
Peritoneal cancer [ICD11:2C51]
Phase 2
Platinum resistant ovarian cancer [ICD11:2C73]
Phase 2
Drug-to-Antibody Ratio
10-15
Antibody Name
XMT-1535
  Antibody Info 
Antigen Name
Sodium-dependent phosphate transport protein 2B (SLC34A2)
  Antigen Info 
Payload Name
Auristatin F hydroxypropylamide (AF-HPA)
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Dolaflexin polymer
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Special Approval(s)
Orphan drug(EMA)
Puchem SID
434150918 , 472419872 , 476262858 , 476269404
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Objective Response Rate (ORR)  NCT03319628
Phase 1/2
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.
Undisclosed  NCT05329545
Phase 3
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).

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Undisclosed  NCT04907968
Phase 1
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).

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Discovered Using Patient-derived Xenograft Model
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Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 58.6
%
Lung cancer PDX model (PDX: CTG-0178)
Tumor Growth Inhibition value (TGI) 
≈ 60.6
%
Lung cancer PDX model (PDX: CTG-0178)
Tumor Growth Inhibition value (TGI) 
≈ 87.4
%
Non-small cell lung cancer PDX model (PDX: CTG-0860)
Tumor Growth Inhibition value (TGI) 
≈ 94.1
%
Lung cancer PDX model (PDX: CTG-0852)
Tumor Growth Inhibition value (TGI) 
≈ 95.4
%
Lung cancer PDX model (PDX: CTG-0852)
Tumor Growth Inhibition value (TGI) 
≈ 96.7
%
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
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 94
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Effective Concentration (EC50) 
0.52
nM
OVCAR-3 cells
Ovarian serous adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
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  Clinical 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  Clinical 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.
Administration Dosage
.
Related Clinical Trial
NCT Number NCT04907968  Clinical 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
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.

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