NAV

Mosunetuzumab

Identification

Summary

Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody used to treat relapsed or refractory follicular lymphoma.

Brand Names
Lunsumio
Generic Name
Mosunetuzumab
DrugBank Accession Number
DB15434
Background

Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody.4 It can recognize and bind two different targets simultaneously, CD20 on cancer B-cells and CD3 on T-cells, allowing it to redirect T-cell cytotoxic activity to cancer cells.1 The standard of care for patients with B-cell lymphoma includes an anti-CD20 monoclonal antibody, such as rituximab, in combination with chemotherapy. However, patients with certain types of B-cell lymphoma, such as follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) or aggressive B-cell lymphoma, have a high probability of relapse or recurrence after treatment.1,3 Mosunetuzumab has the potential to circumvent resistance to rituximab in patients with follicular lymphoma,1,4 and unlike CAR-T therapies such as axicabtagene ciloleucel and tisagenlecleucel, it is an “off-the-shelf” alternative, readily available to patients.5 In June 2022, the European Medicines Agency approved mosunetuzumab for the treatment of adult patients with relapsed or refractory (R/R) FL who have received at least two prior systemic therapies.5 In January 2023, the use of mosunetuzumab was approved by the FDA under accelerated approval based on response rate.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6515H10031N1725O2025S43
Protein Average Weight
146300.0 Da (approximate)
Sequences
>CD3E Heavy Chain
EVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVRQAPGQGLEWIGWIYPGDGNTKY
NEKFKGRATLTADTSTSTAYLELSSLRSEDTAVYYCARDSYSNYYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>CD3E Light Chain
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTR
ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCTQSFILRTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>CD20 Heavy Chain
EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY
NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>CD20 Light Chain
DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR
FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG: Mosunetuzumab (D11463) [Link]
  2. Statement on a nonproprietary name adopted by the USAN Council: Mosunetuzumab [Link]
Download FASTA Format
Synonyms
  • Mosunetuzumab
External IDs
  • BTCT-4465A
  • BTCT4465A
  • RG-7828
  • RG7828
  • RO-7030816
  • RO7030816
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Pharmacology

Indication

Mosunetuzumab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.4,6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRelapsed or refractory follicular lymphoma••••••••••••••••••• ••••• ••• ••••• •••••••• ••••••••••••••••••
Treatment ofRelapsed or refractory follicular lymphoma••••••••••••••••••• ••••• ••• ••••• •••••••• ••••••••••••••••••
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Pharmacodynamics

Mosunetuzumab is an anti-CD20/CD3 bispecific antibody that leads to B-cell depletion (CD19 B-cell counts < 0.07 x 109/L) and hypogammaglobulinemia (IgG levels < 500 mg/dL).4 In patients with aggressive non-Hodgkin's lymphoma (NHL) treated with mosunetuzumab, the overall response rate (ORR) was 37.4%, and the complete remission (CR) rate was 19.5%, while patients with indolent NHL treated with mosunetuzumab had an ORR of 62.7% and a CR rate of 43.3%.2 The response to mosunetuzumab in a high-risk group of patients with progression of follicular lymphoma within 24 months after initiating frontline treatment (n=29) was also beneficial; the ORR was 75.9% and the CR rate was 55.2%.2

Patients treated with mosunetuzumab may develop cytokine release syndrome (CRS), including life-threatening reactions. CRS mainly occurred on days 1 and 15 of cycle 1. To avoid CRS, patients should receive corticosteroids, antipyretics and antihistamines prior to mosunetuzumab therapy.4 Serious infections such as pneumonia, bacteremia, and sepsis or septic shock have been reported in patients treated with mosunetuzumab, and caution should be exercised in patients with a history of recurring or chronic infections. Tumour flare and tumour lysis syndrome (TLS) have also been reported in patients treated with mosunetuzumab.4

Mechanism of action

Mosunetuzumab is a full-length, humanized anti-CD20/CD3 bispecific antibody that targets CD20-expressing B-cells.1,4 Unlike B-cell-targeting monoclonal antibodies, such as rituximab, mosunetuzumab can recognize and bind two different targets, CD20 on cancer B-cells and CD3 on T-cells in a 1:1 ratio.1,2 Mosunetuzumab is a conditional agonist; the targeted killing of CD20-expressing B-cells is observed only when this drug is simultaneously bound to CD20 on B-cells and CD3 on T-cells. Mosunetuzumab recruits T-cells and leads to their activation by promoting the formation of an immunologic synapse between a target B-cell and a cytotoxic T-cell. The activation of T-cells leads to the directed release of perforin and granzymes through the immunologic synapsis, which ultimately induces B-cell lysis and cell death.4

TargetActionsOrganism
AB-lymphocyte antigen CD20
binder
Humans
AT-cell surface glycoprotein CD3 epsilon chain
binder
Humans
Absorption

Between 0.05 and 60 mg, mosunetuzumab follows a dose-proportional pharmacokinetic profile. The population pharmacokinetics of intravenous mosunetuzumab are described with a two-compartment pharmacokinetic model with time-dependent clearance.4 After two cycles of mosunetuzumab (42 days, given by intravenous infusion), patients reached a Cmax of 17.9 µg/mL at the end of dose of Cycle 2 Day 1. The average AUC of two cycles of mosunetuzumab was 126 µg⋅day/mL.4 In patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated with mosunetuzumab, serum concentration reached the Cmax at the end of the intravenous infusion and declined in a bi-exponential fashion.4 The steady-state values of mosunetuzumab were reached at cycle 4 (63 ‒ 84 days). Steady-state AUC and Cmax were 52.9 day⋅μg/mL and 7.02 μg/mL, respectively.6

Mosunetuzumab is expected to have a bioavailability close to 100% when given intravenously. In clinical trials, mosunetuzumab administered subcutaneously had a slow absorption rate and high bioavailability (>75%).2 The pharmacokinetics of mosunetuzumab was similar in Asian and non-Asian subjects. Compared to males, the steady-state clearance of mosunetuzumab in females is marginally lower (approximately 13%), and dose adjustment based on gender is not required.4

Volume of distribution

The estimated central volume of distribution for mosunetuzumab administered via intravenous infusion is 5.49 L.4,6

Protein binding

Mosunetuzumab is a bispecific antibody; therefore, protein binding studies were not carried out.4

Metabolism

Mosunetuzumab is a protein therapeutic; it is expected to be degraded into small peptides and amino acids via catabolic pathways.4

Route of elimination

Since mosunetuzumab is an immunoglobulin G (IgG) antibody, it is expected to be mainly eliminated via intracellular catabolism. Hepatic or renal impairment is not expected to influence the elimination of mosunetuzumab.4

Half-life

Mosunetuzumab has a terminal half-life of 16.1 days,4,6 and an apparent half-life between 6 and 11 days.1

Clearance

The mean steady-state plateau clearance (CLss) of mosunetuzumab is 1.08 L/day, and its baseline clearance (CLbase) is 0.584 L/day.4,6

Adverse Effects
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Toxicity

In case of a mosunetuzumab overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted.4 Patients experiencing an overdose are at an increased risk of severe adverse effects such as cytokine release syndrome (CRS), febrile neutropenia, neutropenia and pneumonia.1,4

Preclinical single- and repeat-dose toxicity studies of up to 26 weeks in duration found that transient CRS was developed mostly after the first dose of mosunetuzumab. Findings suggest that this effect is pharmacologically-mediated and reversible.4 The effect of mosunetuzumab on male and female reproductive organs was evaluated in sexually mature cynomolgus monkeys given an intravenous infusion dose equivalent to the one recommended in patients. Up to 26 weeks, mosunetuzumab did not have an effect on male or female reproductive organs.4 Preclinical studies evaluating the effect of mosunetuzumab on developmental toxicity have not been conducted. Due to the low placental transfer of antibodies during the first trimester, mosunetuzumab is not expected to have a teratogenic effect. However, it can lead to a higher risk of opportunistic infections, which may cause fetal loss.4

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
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interactions in your software
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Mosunetuzumab.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Mosunetuzumab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Mosunetuzumab.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Mosunetuzumab.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Mosunetuzumab.
Food Interactions
Not Available

Products

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International/Other Brands
Lunsumio (Roche)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LunsumioInjection, solution, concentrate1 mgIntravenousRoche Registration Gmb H2022-06-28Not applicableEU flag
LunsumioConcentrate1 mg/1mLIntravenousGenentech, Inc.2022-12-22Not applicableUS flag
LunsumioInjection, solution, concentrate30 mgIntravenousRoche Registration Gmb H2022-06-28Not applicableEU flag
LunsumioConcentrate30 mg/30mLIntravenousGenentech, Inc.2022-12-22Not applicableUS flag

Categories

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
  • Humans and other mammals

Chemical Identifiers

UNII
LDJ89SS0YG
CAS number
1905409-39-3

References

Synthesis Reference

Ast, O., et al. (2018). Bispecific T cell activating antigen binding molecules (U.S. Patent No. 9,914,776 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/e5/93/68/6ded0d607c0070/US9914776.pdf

General References
  1. Budde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, O'Hear C, Huang H, Kwan A, Li CC, Piccione EC, Wei MC, Yin S, Bartlett NL: Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. J Clin Oncol. 2022 Feb 10;40(5):481-491. doi: 10.1200/JCO.21.00931. Epub 2021 Dec 16. [Article]
  2. Salvaris R, Ong J, Gregory GP: Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas. J Pers Med. 2021 Apr 29;11(5). pii: jpm11050355. doi: 10.3390/jpm11050355. [Article]
  3. Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, Yan X, Clark R, Reyes A, Stefanich E, Mai E, Young J, Johnson C, Huseni M, Wang X, Chen Y, Wang P, Wang H, Dybdal N, Chu YW, Chiorazzi N, Scheer JM, Junttila T, Totpal K, Dennis MS, Ebens AJ: Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015 May 13;7(287):287ra70. doi: 10.1126/scitranslmed.aaa4802. [Article]
  4. European Medicines Agency (EMA) Summary of Product Characteristics: Lunsumio (mosunetuzumab) solution for intravenous infusion [Link]
  5. Globe News Wire: European Commission approves Roche’s first-in-class bispecific antibody Lunsumio for people with relapsed or refractory follicular lymphoma [Link]
  6. FDA Approved Drug Products: LUNSUMIO (mosunetuzumab-axgb) injection for intravenous use [Link]
RxNav
2625122
Wikipedia
Mosunetuzumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Not Yet RecruitingTreatmentClassic Follicular Lymphoma / Follicular Lymphoma With Unusual Cytological Features1
3Not Yet RecruitingTreatmentFollicular Lymphoma ( FL)1
3RecruitingTreatmentMarginal Zone Lymphoma (MZL)1
3RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
ConcentrateIntravenous1 mg/1mL
ConcentrateIntravenous30 mg/30mL
Injection, solution, concentrateIntravenous1 mg
Injection, solution, concentrateIntravenous30 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. B-lymphocyte antigen CD20
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. European Medicines Agency (EMA) Summary of Product Characteristics: Lunsumio (mosunetuzumab) solution for intravenous infusion [Link]
Details2. T-cell surface glycoprotein CD3 epsilon chain
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
CD3 chain not specified in drug label. However, the majority of monoclonal antibodies bind to the CD3 epsilon chain.
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. Required for normal immune responses (PubMed:15546002, PubMed:8490660).
Gene Name
CD3E
Uniprot ID
P07766
Uniprot Name
T-cell surface glycoprotein CD3 epsilon chain
Molecular Weight
23147.09 Da
References
  1. Tunnacliffe A, Olsson C, de la Hera A: The majority of human CD3 epitopes are conferred by the epsilon chain. Int Immunol. 1989;1(5):546-50. doi: 10.1093/intimm/1.5.546. [Article]
  2. European Medicines Agency (EMA) Summary of Product Characteristics: Lunsumio (mosunetuzumab) solution for intravenous infusion [Link]

Drug created at May 20, 2019 15:30 / Updated at January 13, 2023 10:08