Atezolizumab

Identification

Summary

Atezolizumab is a monoclonal antibody used to treat advanced or metastatic urothelial carcinoma with disease progression during or up to 12 months after platinum-containing chemotherapy.

Brand Names
Tecentriq
Generic Name
Atezolizumab
DrugBank Accession Number
DB11595
Background

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 In November 2022, the manufacturer (Genentech) voluntarily withdrew the use of atezolizumab for the treatment of urothelial carcinoma, previously approved under the FDA's Accelerated Approval Program. The rest of atezolizumab indications remain unaffected.10

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 has approved indications for the following conditions:11

Non-Small Cell Lung Cancer (NSCLC)

  • as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumours have PD-L1 expression on ≥ 1% of tumour cells, as determined by an FDA-approved test.
  • for the first-line treatment of adult patients with metastatic NSCLC whose tumours have high PD-L1 expression (PD-L1 stained ≥ 50% of tumour cells [TC ≥ 50%] or PD-L1 stained tumour-infiltrating immune cells [IC] covering ≥ 10% of the tumour area [IC ≥ 10%]), as determined by an FDAapproved test, with no EGFR or ALK genomic tumour aberrations.
  • in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations.
  • in combination with paclitaxel protein-bound and carboplatin for the firstline treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations.
  • for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA-approved therapy for NSCLC harbouring these aberrations prior to receiving atezolizumab.

Small Cell Lung Cancer (SCLC)

  • in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Hepatocellular Carcinoma (HCC)

  • in combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.

Melanoma

  • in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Alveolar Soft Part Sarcoma (ASPS)

  • for the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS.
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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMetastatic alveolar soft part sarcoma••••••••••••
Used in combination to treatMetastatic hepatocellular carcinomaRegimen in combination with: Bevacizumab (DB00112)•••••••••••••••••••••••••• •••••
Used in combination to treatMetastatic melanomaRegimen in combination with: Vemurafenib (DB08881), Cobimetinib (DB05239)••••••••••••
Treatment ofMetastatic non-small cell lung cancer•••••••••••••••••••••••••• ••••••••••••••
Treatment ofMetastatic non-squamous non small cell lung cancer•••••••••••••••••••••••• ••••••••••• ••••• ••••••••••••••••••• ••••••••••••
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
inhibitor
antibody
Humans
AProgrammed cell death protein 1
inhibitor
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
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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

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.
AducanumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Aducanumab.
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.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TecentriqInjection, solution1875 mgSubcutaneousRoche Registration Gmb H2024-03-19Not applicableEU flag
TecentriqInjection, solution840 mg/14mLIntravenousGenentech, Inc.2019-03-08Not applicableUS flag
TecentriqInjection, solution, concentrate840 mgIntravenousRoche Registration Gmb H2020-12-16Not applicableEU flag
TecentriqSolution840 mg / 14 mLIntravenousHoffmann La Roche2019-10-16Not applicableCanada flag
TecentriqInjection, solution1200 mg/20mLIntravenousGenentech, Inc.2016-05-18Not applicableUS flag

Categories

ATC Codes
L01FF05 — 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
Affected organisms
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Mann, Janelle: Atezolizumab (Tecentriq®) Oncology Times. 2017 Feb 25;39(4):31. [Article]
  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. [Article]
  7. FDA Approved Drug Products: Atezolizumab Intravenous Injection [Link]
  8. Roche News Release: Tecentriq as adjuvant treatment for NSCLC [Link]
  9. European Commission approves Roche’s Tecentriq as adjuvant treatment for a subset of people with early-stage non-small cell lung cancer [Link]
  10. BioSpace: Roche Withdraws Tecentriq for Bladder Cancer Indication [Link]
  11. FDA Approved Drug Products: TECENTRIQ (atezolizumab) injection, for intravenous use (December 2022_2) [Link]
  12. FDA Approved Drug Products: Tecentriq (atezolizumab) injection for intravenous use (May 2023) [Link]
KEGG Drug
D10773
PubChem Substance
347911207
RxNav
1792776
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Atezolizumab
FDA label
Download (245 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4CompletedDiagnosticLung Cancer1somestatusstop reasonjust information to hide
4CompletedTreatmentNon-Small Cell Lung Carcinoma1somestatusstop reasonjust information to hide
4Not Yet RecruitingTreatmentUnresectable Hepatocellular Carcinoma (HCC)1somestatusstop reasonjust information to hide
4RecruitingTreatmentHepatocellular Carcinoma / Liver Cancer1somestatusstop reasonjust information to hide
4RecruitingTreatmentInfusion related reaction / Oncology1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous1200 mg/20mL
Injection, solutionIntravenous840 mg/14mL
Injection, solutionSubcutaneous1875 mg
Injection, solution, concentrateIntravenous
Injection, solution, concentrateIntravenous1200 mg
Injection, solution, concentrateIntravenous60 mg/1ml
Injection, solution, concentrateIntravenous840 mg
Injection, solution, concentrateIntravenous; Parenteral1200 MG
Injection, solution, concentrateIntravenous; Parenteral840 MG
SolutionIntravenous1200 mg / 20 mL
SolutionIntravenous1200.000 mg
SolutionIntravenous840 mg / 14 mL
Injection, solution, concentrate1200 mg/20ml
Injection, solution, concentrateIntravenous60 mg/ml
Injection, solution, concentrate840 mg/14ml
SolutionIntravenous1200 mg
SolutionIntravenous840 mg/14ml
SolutionSubcutaneous125 mg / mL
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

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. [Article]
  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. [Article]
  3. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]
  4. FDA Approved Drug Products: Atezolizumab Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Signal transducer activity
Specific Function
Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. ...
Gene Name
PDCD1
Uniprot ID
Q15116
Uniprot Name
Programmed cell death protein 1
Molecular Weight
31646.635 Da
References
  1. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]

Drug created at May 19, 2016 15:42 / Updated at May 19, 2023 23:20