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Alveltamig

Alias: ZG006
Alveltamig (ZG006) is a trispecific anti-T cell adaptor protein (Tri-TE) that targets Delta-like ligand 3 (DLL3) and CD3.
Alveltamig
Alveltamig Chemical Structure Product category: CD3
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
Other Sizes
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Product Description
Alveltamig (ZG006) is a trispecific anti-T cell adaptor (Tri-TE) that targets Delta-like ligand 3 (DLL3) and CD3. Alveltamig possesses two distinct DLL3 epitopes and bridges tumor cells and T cells by strongly binding to DLL3 on tumor cells and CD3 on T cells, thereby mediating T cell-specific killing of DLL3-expressing tumor cells. Alveltamig can be used in research on small cell lung cancer (SCLC) or neuroendocrine carcinoma (NEC).
Alveltamig (ZG006) is a first-in-class, trispecific T-cell engager (Tri-TCE) designed for DLL3-targeted therapy. It is structured with two binding arms for the tumor antigen DLL3 (dual epitope binding) and one arm for the CD3 receptor on T cells, creating a 2:1 binding configuration. It received FDA Orphan Drug Designation and Breakthrough Therapy Designation for SCLC in both the U.S. and China. A strategic collaboration with AbbVie was announced for development ex-China.
Biological Activity I Assay Protocols (From Reference)
Targets
Alveltamig targets Delta-like ligand 3 (DLL3), a Notch ligand that is highly expressed on the cell surface of neuroendocrine tumors, including small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), but has minimal expression on normal adult tissues. As a trispecific antibody, it engages two distinct non-overlapping epitopes on DLL3 and the CD3 epsilon subunit on T cells. By strongly bridging T cells to DLL3-expressing tumor cells, it induces T-cell activation, proliferation, and cytotoxic granule release (perforin, granzymes), leading to tumor cell lysis. The dual-epitope targeting is designed to drive efficacy even against tumors with low DLL3 expression.
ln Vitro
In preclinical studies, Alveltamig demonstrates high binding specificity and T-cell activation only in the presence of DLL3-positive tumor cells. Cell-killing assays show potent activity against various DLL3-expressing tumor cell lines. The 2:1 configuration results in a high degree of specificity, reducing the risk of off-tumor toxicity compared to traditional 1:1 bispecific T-cell engagers. Detailed in vitro potency (EC50/IC50) data are not provided in the search results.
ln Vivo
In Phase I/II clinical trials, Alveltamig has demonstrated robust and durable efficacy in patients with advanced SCLC. In a Phase II study, the confirmed objective response rate (ORR) was 53.3% (10 mg Q2W) and 56.7% (30 mg Q2W), with a disease control rate (DCR) of 73.3% for both groups. The drug is generally well-tolerated, with the most common adverse events being pyrexia (fever) and manageable grade 1/2 cytokine release syndrome (CRS). It is currently being evaluated in clinical trials as a monotherapy and in combination with other agents, including anti-PD-1 antibodies.
Enzyme Assay
Non-cellular binding assays are used to characterize Alveltamig. A standard surface plasmon resonance (SPR) protocol involves immobilizing recombinant human DLL3 and CD3 proteins on a sensor chip. Alveltamig is then flowed over the chip at concentrations ranging from 0.1-100 nM, and association and dissociation rates are measured to calculate KD values. The 2:1 binding stoichiometry can be confirmed via analytical size-exclusion chromatography (SEC) and biolayer interferometry (BLI).
Cell Assay
For cell-based activity assays, a co-culture system is used. Reporter cells (e.g., Jurkat T cells expressing a luciferase reporter under a T-cell activation element) are co-cultured with target cells (DLL3-expressing tumor cells). Alveltamig is added at 0.01-100 pM. After 6-24 h, the plate is read for bioluminescence to quantify T-cell activation. For direct target cell killing, PBMCs from healthy donors are co-cultured with DLL3-positive tumor cells, and target cell death is measured by LDH release or flow cytometry. Cytokine release (IFN-gamma, IL-2, TNF-alpha) can also be measured via ELISA.
Animal Protocol
Standard in vivo efficacy studies use immunodeficient mice (e.g., NSG) engrafted with human DLL3-positive tumor cells (e.g., SCLC cell lines) and reconstituted with human PBMCs or purified T cells. After tumor engraftment, mice receive Alveltamig intravenously at doses ranging from 0.1 to 10 mg/kg once weekly for 3-4 weeks. Control groups include vehicle and non-targeting control antibodies. Tumor volume is measured with calipers twice weekly. Pharmacodynamic markers include T-cell infiltration into tumors (flow cytometry/IHC) and cytokine levels in plasma. The study typically lasts 28-45 days.
ADME/Pharmacokinetics
As a bispecific T-cell engager (molecular weight ~150 kDa), Alveltamig is administered via intravenous infusion. It has a long terminal half-life consistent with monoclonal antibodies, typically 5-10 days in humans. The volume of distribution is limited (primarily to the vascular space), clearance is low (primarily via proteolytic catabolism), and oral bioavailability is zero. No formal drug-drug interaction studies are available. For storage, it is supplied as a solution and must be stored at -80degC.
Toxicity/Toxicokinetics
In clinical trials, Alveltamig has shown a manageable safety profile. The most common adverse events are pyrexia (fever) and cytokine release syndrome (CRS), which were primarily Grade 1-2 and manageable with supportive care. No dose-limiting toxicities or unexpected safety signals have been reported. Grade 3-4 events are infrequent. Standard safety precautions for laboratory handling of research-grade protein constructs include the use of PPE (gloves, lab coat) and working in a biological safety cabinet.
References

[1]. A phase 1 dose escalation and expansion study of ZG006, a trispecific T cell engager targeting CD3/DLL3/DLL3, as monotherapy in patients with refractory small cell lung cancer or neuroendocrine carcinoma[J]. 2025.

Additional Infomation
Alveltamig (ZG006) is an INN drug candidate. Its molecular weight is approximately 150 kDa. The drug's structure is a trispecific T-cell engager with two anti-DLL3 variable domains and one anti-CD3 domain. Developed by Suzhou Zelgen Biopharmaceuticals. Broad patents for composition of matter have been granted. It has received Orphan Drug Designation and Breakthrough Therapy Designation from the FDA and NMPA for SCLC. Not for human therapeutic use outside clinical trials.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Appearance
Typically exists as solids at room temperature
Synonyms
ZG006
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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