Antibody Information

General Information of This Antibody
Antibody ID
ANI0CQMLX
Antibody Name
Cirmtuzumab
Organization
Oncternal Therapeutics, Inc.
Indication
Sleeve cell lymphoma; Marginal zone B-cell lymphoma; B-cell chronic lymphocytic leukemia
Synonyms
UC-961; Zilovertamab
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Inactive tyrosine-protein kinase transmembrane receptor ROR1 (ROR1)
  Antigen Info 
ChEMBI ID
CHEMBL4297728
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
QVQLQESGPGLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWMGSFDPYDGGSSY
NQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARGWYYFDYWGHGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
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Light Chain Sequence
DIVMTQTPLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLIYSGSTLQSGIPP
RFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPYTFGEGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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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
Zilovertamab vedotin [Phase 2/3]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
30.00%
Patients Enrolled
Patients with diffuse large B-cell lymphoma (DLBCL), PET-positive disease, and ECOG PS of 0-2. Pts must have received 2 prior lines of therapy.
Administration Dosage
2.50 mg/kg IV Q3W.
Related Clinical Trial
NCT Number NCT05144841  Clinical Status Phase 2
Clinical Description
A phase 2 open-label clinical study to evaluate the efficacy and safety of zilovertamab vedotin (MK-2140) in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-004).
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
47.00% (MCL)
60.00% (DLBCL)
Patients Enrolled
Patients with tumor histologies of mantle cell lymphoma (MCL), chronic lymphocytic leukemia, diffuse large B-cell lymphoma (DLBCL). Patients had received a median of four previous drug and/or cellular therapies.
Administration Dosage
2.50 mg/kg every 3 week.
Related Clinical Trial
NCT Number NCT03833180  Clinical Status Phase 1
Clinical Description
A phase 1 dose-escalation and cohort-expansion study of VLS-101 in subjects with hematological malignancies (waveline-001).
Experiment 3 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Patients with diffuse large B-cell lymphoma (DLBCL) after 1 line of prior therapy (cohort A) or 2 lines of prior therapy (cohort B).
Administration Dosage
ZV (1.50, 1.75, 2.00, 2.25, and 2.50 mg/kg) with gemcitabine-oxaliplatin + rituximab (R-GemOx).
Related Clinical Trial
NCT Number NCT05139017  Clinical Status Phase 2/3
Clinical Description
A phase 2/3 multicenter, open-label, randomized, active-control study of zilovertamab vedotin (MK-2140) in combination with standard of care in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-003).
Experiment 4 Reporting the Activity Date of This ADC [4]
Patients Enrolled
Patients with mantle cell lymphoma (MCL), Richter's transformation (RT), chronic lymphocytic leukemia (CLL), or follicular lymphoma (FL), relapsed or refractory (R/R) disease, ECOG performance status of 0 to 2.
Administration Dosage
ZV 2.0 to 2.50 mg/kg IV Q3W.
Related Clinical Trial
NCT Number NCT05458297  Clinical Status Phase 2
Clinical Description
A multicenter, open-label, phase 2 basket study to evaluate the safety and efficacy of MK-2140 as a monotherapy and in combination in participants with aggressive and indolent B-cell malignancies.
Experiment 5 Reporting the Activity Date of This ADC [5]
Patients Enrolled
Patients with previously untreated histologically confirmed diffuse large B-cell lymphoma (DLBCL), PET-positive and ECOG PS of 0 or 1.
Administration Dosage
ZV was 1.75 mg/kg (modified to 1.50, 2.00, 2.25, or 2.50 mg/kg) administered as an intravenous infusion every 3 weeks (Q3W) in combination with R-CHP.
Related Clinical Trial
NCT Number NCT05406401  Clinical Status Phase 2
Clinical Description
A multicenter, open-label, phase 2 dose escalation and confirmation, and efficacy expansion study of zilovertamab vedotin (MK-2140) in combination with r-chp in participants with DLBCL (waveline).
Experiment 6 Reporting the Activity Date of This ADC [6]
Patients Enrolled
Patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors.
Related Clinical Trial
NCT Number NCT05562830  Clinical Status Phase 1/2
Clinical Description
A phase 1/2 open-label rolling-arm umbrella platform study of investigational agents with or without pembrolizumab in participants with PD-1/L1 refractory locally advanced or metastatic urothelial carcinoma (keymaker-u04): substudy 04a.
Experiment 7 Reporting the Activity Date of This ADC [7]
Related Clinical Trial
NCT Number NCT04504916  Clinical Status Phase 1
Clinical Description
A phase 2 study of VLS-101 in patients with solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 30) Negative ROR1 expression (ROR1-)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 30) Negative ROR1 expression (ROR1-)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
Experiment 3 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.80% (Day 47) High ROR1 expression (ROR1+++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: IP867/17)
Experiment 4 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.90% (Day 57) Moderate ROR1 expression (ROR1++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
Experiment 5 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 47) High ROR1 expression (ROR1+++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: IP867/17)
Experiment 6 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 47) High ROR1 expression (ROR1+++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
Experiment 7 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 47) High ROR1 expression (ROR1+++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
Experiment 8 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 57) Moderate ROR1 expression (ROR1++)
Method Description
VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model Richter syndrome PDX model (PDX: RS9737)
References
Ref 1 Open-label, active-control, phase 2/3 study of zilovertamab vedotin plus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2022 40:16_suppl, TPS7592-TPS7592.
Ref 2 Phase 2 study of zilovertamab vedotin (ZV) in combination with cyclophosphamide, doxorubicin, and prednisone plus rituximab (R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2023 41:16_suppl, TPS7589-TPS7589.
Ref 3 A phase I study of CPI-0610, a bromodomain and extra terminal protein (BET) inhibitor in patients with relapsed or refractory lymphoma. Ann. Oncol. 2018 Mar; 29(3):Supplement I117.
Ref 4 BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. J Clin Oncol. 2023 41:16_suppl, 3001-3001.
Ref 5 A phase 2 study of the safety and efficacy of zilovertamab vedotin as monotherapy or in combination in patients (pts) with aggressive and indolent B-cell malignancies. J Clin Oncol. 2023 41:16_suppl, TPS7595-TPS7595.
Ref 6 A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A, NCT05562830
Ref 7 A Phase 2 Study of VLS-101 in Patients With Solid Tumors, NCT04504916
Ref 8 ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models. Blood. 2021 Jun 17;137(24):3365-3377.

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