Antibody Information

General Information of This Antibody

Antibody ID	ANI0GRHJC
Antibody Name	Azintuxizumab
Organization	AbbVie, Inc.
Indication	Multiple Myeloma
Synonyms	ABBV-383; PR-1471272 Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Chimeric IgG1-kappa
Antigen Name	SLAM family member 7 (SLAMF7)	Antigen Info
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	EVQLVESGGGLVQPGGSLRLSCAASGFTFSDYYMAWVRQAPGKGLEWVASINYDGSSTYY VDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDRGYYFDYWGQGTTVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Varible Domain	EVQLVESGGGLVQPGGSLRLSCAASGFTFSDYYMAWVRQAPGKGLEWVASINYDGSSTYY VDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDRGYYFDYWGQGTTVTVSS Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Hinge Region	EPKSCDKTHTCPPCP Click to Show/Hide
Heavy Chain CDR 1	GFTFSDYY Click to Show/Hide
Heavy Chain CDR 2	INYDGSST Click to Show/Hide
Heavy Chain CDR 3	ARDRGYYFDY Click to Show/Hide
Light Chain Sequence	DVVMTQTPLSLSVTPGQPASISCRSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRF SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCSQSTHVPPFTFGGGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain Varible Domain	DVVMTQTPLSLSVTPGQPASISCRSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRF SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCSQSTHVPPFTFGGGTKVEIK Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain CDR 1	QSLVHSNGNTY Click to Show/Hide
Light Chain CDR 2	KVS Click to Show/Hide
Light Chain CDR 3	SQSTHVPPFT Click to Show/Hide

Each Antibody-drug Conjugate Related to This Antibody

Full Information of The Activity Data of The ADC(s) Related to This Antibody

Azintuxizumab vedotin [Phase 1 (discontinued)]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 5 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Objective Response Rate (ORR)	10.67%
Patients Enrolled	Relapsed or refractory multiple myeloma (RRMM) and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; were not eligible for stem cell/bone marrow transplant or had refused stem cell/bone marrow transplant, or had relapsed after autologous or allogeneic stem cell/bone marrow transplant.
Administration Dosage	ABBV-838 (3+3 design) intravenously starting from 0.60 mg/kg up to 6.00 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel.
*Related Clinical Trial*
NCT Number	NCT02462525	Clinical Status	Phase 1
Clinical Description	A multicenter, phase 1/1b, open-label, dose-escalation study of ABBV-838, an antibody drug conjugate, in subjects with relapsed and refractory multiple myeloma.
Primary Endpoint	OrR=10.67% (N=8/75, 95% Cl 4.7-19.9), very good partial response (VGPR)=2.67% (N=2), PR=8.00% (N=6). Median DOR=4 months.
Other Endpoint	The MTD was not reached. The selected recommended dose for the expansion cohort was 5.00 mg/kg Q3W.
Experiment 2 Reporting the Activity Date of This ADC				[2]
*Related Clinical Trial*
NCT Number	NCT02951117	Clinical Status	Phase 1
Clinical Description	A phase 1b, open label, multicenter, dose escalation study of venetoclax and ABBV-838 combination therapy with dexamethasone in subjects with relapsed or refractory multiple myeloma.
Experiment 3 Reporting the Activity Date of This ADC				[3]
*Related Clinical Trial*
NCT Number	NCT02462525	Clinical Status	Phase 1
Clinical Description	A multicenter, phase 1/1b, open-label, dose-escalation study of ABBV-838, an antibody drug conjugate, in subjects with relapsed and refractory multiple myeloma.
Experiment 4 Reporting the Activity Date of This ADC				[4]
Patients Enrolled	Eligible participants had relapsed/refractory multiple myeloma (≥3 prior lines including proteasome inhibitors/immunomodulatory drugs) with measurable disease, adequate organ function, and LVEF ≥45% if applicable. Exclusions included recent anticancer therapy (<21 days), solid tumors, unresolved toxicities (≥Grade 2), uncontrolled conditions, active infections, strong CYP3A4 inhibitors, HIV/hepatitis, or prior pomalidomide exposure for combination-arm participants. Click to Show/Hide
Administration Dosage	Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel.
*Related Clinical Trial*
NCT Number	NCT02462525	Clinical Status	PHASE1
Clinical Description	A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
Primary Endpoint	Pharmacokinetic evaluation of ABBV-838 included maximum plasma concentration (Cmax, ng/ml) measured at multiple timepoints (Cycles 1-3) and maximum tolerated dose assessment (over ~2 years), with dose-limiting toxicities monitored to determine safety thresholds.
Other Endpoint	Preliminary efficacy of ABBV-838 monotherapy was based on International Myeloma Working Group (IMWG) response criteria, assessed radiologically at screening, Cycle 1 Day 15, and periodically thereafter (~3 years).
Experiment 5 Reporting the Activity Date of This ADC				[5]
Patients Enrolled	Eligible participants had relapsed/refractory multiple myeloma (≥2 prior therapies including IMiD + proteasome inhibitor), measurable disease (serum/urine M-protein or sFLC), and ECOG ≤1 (dose escalation) or ≤2 (expansion). Exclusions included recent anti-myeloma therapy (within 5 half-lives/14 days for non-mAbs; 6 weeks for mAbs), uncontrolled comorbidities, or corticosteroid use (≥4 mg/day dexamethasone within 3 weeks). Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT02951117	Clinical Status	PHASE1
Clinical Description	A Phase 1b, Open Label, Multicenter, Dose Escalation Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Primary Endpoint	The study aims to determine the maximum tolerated dose (MTD) and recommended phase two dose (RPTD) of venetoclax + ABBV-838 + dexamethasone during dose escalation (1 cycle, 21-28 days). Safety will be monitored via adverse events (AEs) for ~2 years post-enrollment.
Other Endpoint	Pharmacokinetic parameters (Cmax, Tmax, AUC) of venetoclax and ABBV-838 will be assessed over ~43-57 days, alongside efficacy (ORR per IMWG criteria), toxin levels (MMAE), total mAb, and MRD negativity (10^-5 threshold by NGS). Terminal elimination (t1/2, beta) of ABBV-838 will be analyzed on Cycle 1 Day 1.

References

Ref 1	First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. Clin Cancer Res. 2020 May 15;26(10):2308-2317.
Ref 2	A Phase 1b, Open Label, Multicenter, Dose Escalation Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma, NCT02951117
Ref 3	A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma, NCT02462525
Ref 4	Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
Ref 5	A Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Participants With Multiple Myeloma Whose Cancer Has Come Back or Had No Response to Recent Cancer Treatment

Antibody Information

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)