Atezolizumab

Identification

Name
Atezolizumab
Accession Number
DB11595
Description

Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers.2,7 This medication is reserved for patients whose tumors express PD-L1, cannot receive platinum based chemotherapy, or whose tumors do not respond to platinum based chemotherapy.7 Atezolizumab was granted FDA approval on 18 October 2016.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
145000.0 Da
Sequences
>Heavy Chain Sequence
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYY
ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYAST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain Sequence
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Atezolizumab
External IDs
  • MPDL 3280A
  • MPDL-3280A
  • MPDL3280A
  • RG-7446
  • RG7446

Pharmacology

Indication

Atezolizumab is indicated to treat locally or advanced metastatic urothelial carcinoma in patients ineligible for cicplatin-containing chemotherapy with tumors expressing PD-L1, in patients ineligible for cisplatin-containing chemotherapy irrespective of PD-L1, have disease progression following platinum containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant chemotherapy.7

Atezolizumab is also indicated first line for non small cell lung cancer in combination with bevacizumab, paclitaxel, and carboplatin with no EGFR or ALK genomic abnormalities.7 It can be used in patients with disease progression during or after platinum containing chemotherapy even if they have EGFR and ALK abnormalities.7

Atezolizumab is indicated in combination with paclitaxel protein-bound to treat locally advanced or metastatic triple negative breast cancer expressing PD-L1.7

Finally, atezolizumab is indicated in combination with carboplatin and etoposide as first line treatment for extensive stage small cell lung cancer.7

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers.2,7 This drug has a long duration of action as it is usually given every 3-4 weeks.7 Atezolizumab should not be used in patients with immune mediated penumonitis, hepatitis, colitis, and some endocrinopathies.7

Mechanism of action

Atezolizumab is a humanized IgG antibody that binds PD-L1, preventing its interaction with PD-1 and B7-1.2 Preventing the interaction of PD-L1 and PD-1 removes inhibition of immune responses such as the anti-tumor immune response but not antibody dependent cellular cytotoxicity.7

TargetActionsOrganism
AProgrammed cell death 1 ligand 1
antibody
Humans
Absorption

Pharmacokinetic analysis was performed in patients with metastatic urothelial carcinoma.3 In these patients, the AUC was 2.19-2.73day*µg/mL/mg, the Cmax was 0.27-0.35µg/mL/mg, and the Cmin was 0.004-0.008µg/mL/mg.3

Volume of distribution

The volume of distribution of atezolizumab is 6.91L.1,3

Protein binding

Monoclonal antibodies are not expected to bind to proteins in plasma they are not designed to target.

Metabolism

Monoclonal antibodies are broken down into smaller polypeptides and amino acids.4

Route of elimination

Atezolizumab is not renally excreted.5

Half-life

The half life of atezolizumab is 27 days.1,3

Clearance

The clearance of atezolizumab is 0.200L/day.1,3

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Most common adverse reactions (≥ 20% of patients) included: fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation.

Overdose data for atezolizumab is scarce6 but the most common adverse reactions are fatigue, nausea, cough, dyspnea, decreased appetite, alopecia, constipation, diarrhea, peripheral neuropathies, anemia, headache, neutropenia, and vomiting.7

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Atezolizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Atezolizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Atezolizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Atezolizumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Atezolizumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Atezolizumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Atezolizumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Atezolizumab.
AvelumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Avelumab.
BasiliximabThe risk or severity of adverse effects can be increased when Basiliximab is combined with Atezolizumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TecentriqSolution840 mgIntravenousHoffmann La Roche2019-10-16Not applicableCanada
TecentriqInjection, solution1200 mg/20mLIntravenousGenentech, Inc.2016-05-18Not applicableUs
TecentriqSolution1200 mgIntravenousHoffmann La Roche2017-05-02Not applicableCanada
TecentriqInjection, solution840 mg/14mLIntravenousGenentech, Inc.2019-03-08Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XC32 — Atezolizumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
52CMI0WC3Y
CAS number
1380723-44-3

References

General References
  1. Markham A: Atezolizumab: First Global Approval. Drugs. 2016 Aug;76(12):1227-32. doi: 10.1007/s40265-016-0618-8. [PubMed:27412122]
  2. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4. [PubMed:26952546]
  3. Stroh M, Winter H, Marchand M, Claret L, Eppler S, Ruppel J, Abidoye O, Teng SL, Lin WT, Dayog S, Bruno R, Jin J, Girish S: Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma. Clin Pharmacol Ther. 2017 Aug;102(2):305-312. doi: 10.1002/cpt.587. Epub 2017 Jun 9. [PubMed:27981577]
  4. Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [PubMed:16478695]
  5. Mann, Janelle: Atezolizumab (Tecentriq®) Oncology Times. 2017 Feb 25;39(4):31.
  6. Raschi E, Mazzarella A, Antonazzo IC, Bendinelli N, Forcesi E, Tuccori M, Moretti U, Poluzzi E, De Ponti F: Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System. Target Oncol. 2019 Apr;14(2):205-221. doi: 10.1007/s11523-019-00632-w. [PubMed:30927173]
  7. FDA Approved Drug Products: Atezolizumab Intravenous Injection [Link]
KEGG Drug
D10773
PubChem Substance
347911207
RxNav
1792776
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Atezolizumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (245 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4Approved for MarketingNot AvailableTransitional Cell Carcinoma1
4RecruitingDiagnosticLung neoplasm malignant1
4RecruitingTreatmentMalignancies1
3Active Not RecruitingTreatmentAbdominal wall neoplasm / Fallopian Tube Cancer / Ovarian Cancer1
3Active Not RecruitingTreatmentAdvanced BRAFV600 Wild-type Melanoma1
3Active Not RecruitingTreatmentCarcinoma, Non-Squamous Non-Small Cell Lung1
3Active Not RecruitingTreatmentHepatocellular Carcinoma1
3Active Not RecruitingTreatmentInvasive Ductal Breast Carcinoma1
3Active Not RecruitingTreatmentMelanoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous1200 mg/20mL
Injection, solutionIntravenous840 mg/14mL
SolutionIntravenous1200 mg
SolutionIntravenous840 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)78 Ji-Hee, et al. Front Immunol, 7:394 (2016)
boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility50mg/mL Human IgG purified. Product Information
isoelectric point6.6-7.2 Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Not Available
Specific Function
Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell ...
Gene Name
CD274
Uniprot ID
Q9NZQ7
Uniprot Name
Programmed cell death 1 ligand 1
Molecular Weight
33275.095 Da
References
  1. Markham A: Atezolizumab: First Global Approval. Drugs. 2016 Aug;76(12):1227-32. doi: 10.1007/s40265-016-0618-8. [PubMed:27412122]
  2. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4. [PubMed:26952546]
  3. FDA Approved Drug Products: Atezolizumab Intravenous Injection [Link]

Drug created on May 19, 2016 09:42 / Updated on August 05, 2020 23:35

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