Antibody Information

General Information of This Antibody
Antibody ID
ANI0MRPNB
Antibody Name
Lifastuzumab
Organization
Genentech, Inc.
Indication
Neoplasms
Synonyms
MNIB2126A
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Sodium-dependent phosphate transport protein 2B (SLC34A2)
  Antigen Info 
ChEMBI ID
CHEMBL3545260
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVATIGRVAFHTYY
PDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHRGFDVGHFDFWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Light Chain Sequence
DIQMTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGKAPKLLIYRVSNRF
SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQGSFNPLTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Lifastuzumab vedotin [Terminated in phase 2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Partial Response (PR)
7.84% (patients with NSCLC, active doses 1.8 mg/kg)
45.83% (patients with PROC, active doses 1.8 mg/kg)
25.00% (1.8 mg/kg, in the NSCLC cohorts)
6.67% (2.4 mg/kg, in the NSCLC cohorts)
Patients Enrolled
Incurable, locally advanced, or metastatic disease (non-squamous NSCLC or non-mucinous PROC) that had progressed on or following prior chemotherapy and for which no standard therapy existed, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Administration Dosage
The starting dose for LIFA was 0.20 mg/kg administered by intravenous infusion (IV) every 3 weeks (Q3W), in this 3+3 dose-escalation design, followed by cohort expansion at the recommended phase II dose (RP2D).
Related Clinical Trial
NCT Number NCT01911598  Clinical Status Phase 1a
Clinical Description
A phase 1b open-label study of the safety and pharmacokinetics of MEHD7945A in combination with either cisplatin and 5-fu or paclitaxel and carboplatin in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
Primary Endpoint
The MTD was not reached on this study and the maximum administered dose (MAD) was 2.80 mg/kg. Upon evaluation of the safety data of the 6 patients treated at the MAD, the dose of 2.40 mg/kg was established as the RP2D.
Other Endpoint
At active doses 1.80 mg/kg, partial responses were observed in four of 51 (7.84%) patients with NSCLC and 11 of 24 (45.83%) patients. In the NSCLC cohorts, PRs were seen in 1 of 4 (25.00%) at 1.80 mg/kg and in 3 of 45 (6.67%) patients at 2.40 mg/kg, mDoR=161 days. In PROC, PRs were seen at 1.80 mg/kg in one of two (50.00%), at 2.40 mg/kg in seven of 18 (38.89%), and at 2.80 mg/kg in three of four (75.00%) patients; mDoR=342 days.

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Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
34.00% (ITT population)
36.00% (NaPi2bx high patients)
Patients Enrolled
Advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer that had progressed or relapsed within 6months of the most recent treatment with a platinum-containing chemotherapy regimen and for whom PLD was considered an appropriate therapy.
Administration Dosage
2.40 mg/kg, intravenously, every 3 weeks (Q3W).
Related Clinical Trial
NCT Number NCT01991210  Clinical Status Phase 2
Clinical Description
A randomized, open-label, multicenter, phase 2 trial evaluating the safety and activity of DNIB0600A compared to pegylated liposomal doxorubicin administered intravenously to patients with platinum-resistant ovarian cancer.
Primary Endpoint
The stratified PFS hazard ratio was 0.78 (95% CI,0.46-1.31; p=0.34) with a median PFS of 5.30 vs. 3.10 months (LIFA vs. PLD arm,respectively) in the ITT population, and 0.71 (95% CI,0.40-1.26; p=0.24) with a median PFS of 5.30 vs. 3.40 months (LIFA vs. PLD arm,respectively) in NaPi2bxhigh patients. The objective response rate (ORR) was 34.00% (95% CI,22.00-49.00%,LIFA) vs. 15.00% (95% CI, 7.00-28.00%,PLD) in the ITT population (p=0.03), and 36.00% (95% CI, 22.00-52.00%,LIFA) vs.14.00% (95% CI,6.00-27.00%,PLD) in NaPi2bxhigh patients (p=0.02).

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Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
34.00% (all)
36.00% (SLC34A2 2+/3+)
Patients Enrolled
Platinum-resistant patients with histologically documented advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Administration Dosage
2.40 mg/kg, intravenously, every 3 weeks (Q3W).
Related Clinical Trial
NCT Number NCT01991210  Clinical Status Phase 2
Clinical Description
A randomized, open-label, multicenter, phase 2 trial evaluating the safety and activity of DNIB0600A compared to pegylated liposomal doxorubicin administered intravenously to patients with platinum-resistant ovarian cancer.
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR)
25.00% (1.8 mg/kg NSCLC)
7.00% (2.4 mg/kg NSCLC)
50.00% (1.8 mg/kg PROC)
39.00% (2.4 mg/kg PROC)
75.00% (2.8 mg/kg PROC)
Patients Enrolled
Patients with nonsmall cell lung cancer (NSCLC) and platinum-resistant ovarian cancer (PROC).
Administration Dosage
Dose-escalation: 0.20-2.80 mg/kg once every 3 weeks, dose-expansion: 4 mg/kg once every 3 weeks.
Related Clinical Trial
NCT Number NCT01363947  Clinical Status Phase 1
Clinical Description
A phase 1, open-label study of the safety and pharmacokinetics of escalating doses of DNIB0600A in patients with non-small cell lung cancer and platinum-resistant ovarian cancer.
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Complete Remission (CR)
58.54%
Patients Enrolled
Polycystic ovary syndrome (PSOC) patients (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer) with documented radiographic progression or relapse according to RECIST v1.1.
Administration Dosage
The starting dose of LIFA was 1.20 mg/kg, once every 3 weeks (Q3W) on the first day of 21-day cycles, traditional 3 + 3 study design.
Related Clinical Trial
NCT Number NCT01995188  Clinical Status Phase 1b
Clinical Description
A phase 1b, open-label, dose-escalation study of the safety and pharmacology of DNIB0600A in combination with carboplatin (with or without bevacizumab) in patients with platinum-sensitive ovarian cancer or non-squamous non-small cell lung cancer.
Primary Endpoint
The median duration of progression-free survival was 10.71 months (95% CI: 8.54,13.86) with confirmed complete/partial responses in 24 (58.54%) patients.
Other Endpoint
The maximum tolerated dose was not reached. The recommended phase 2 dose (RP2D) was LIFA 2.40 mg/kg + carboplatin AUC6 (cycles 16), with or without bevacizumab 15 mg/kg.
Experiment 6 Reporting the Activity Date of This ADC [6]
Related Clinical Trial
NCT Number NCT01995188  Clinical Status Phase 1
Clinical Description
A phase 1b, open-label, dose-escalation study of the safety and pharmacology of DNIB0600A in combination with carboplatin (with or without bevacizumab) in patients with platinum-sensitive ovarian cancer or non-squamous non-small cell lung cancer.
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 [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 19.60% (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 2 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 25.40% (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 3 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 27.60% (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 4 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.30% (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)
Experiment 5 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.70% (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 [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.80% (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)
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) ≈ 41.20% (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
References
Ref 1 Phase Ia Study of Anti-NaPi2b Antibody-Drug Conjugate Lifastuzumab Vedotin DNIB0600A in Patients with Non-Small Cell Lung Cancer and Platinum-Resistant Ovarian Cancer. Clin Cancer Res. 2020 Jan 15;26(2):364-372.
Ref 2 Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study. Ann Oncol. 2018 Apr 1;29(4):917-923.
Ref 3 Deka biosciences biotechnology company product pipeline.
Ref 4 ADC review: basic information about LCB14-2NM.
Ref 5 Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2020 Sep;158(3):631-639.
Ref 6 A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of DNIB0600A in Combination With Carboplatin (With or Without Bevacizumab) in Patients With Platinum-Sensitive Ovarian Cancer or Non-Squamous Non-small Cell Lung Cancer, NCT01995188
Ref 7 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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