(A chain)
QVQLVESGGG VVQPGRSLRL SCAASGFTFS TYGMHWVRQA PGKGLEWVAV IWDDGSYKYY
GDSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARDG ITMVRGVMKD YFDYWGQGTL
VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA
VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSCDK THTCPPCPAP
ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV EVHNAKTKPR
EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ PREPQVYTLP
PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFLLYSKLTV
DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK
(B chain)
QVQLVQSGAE VKKPGASVKV SCETSGYTFT SYGISWVRQA PGHGLEWMGW ISAYNGYTNY
AQKLQGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARDL RGTNYFDYWG QGTLVTVSSA
STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG
LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKRVEPK SCDKTHTCPP CPAPELLGGP
SVFLFPPKPK DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS
TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV YTLPPSREEM
TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ
QGNVFSCSVM HEALHNHYTQ KSLSLSPGK
(C chain)
AIQLTQSPSS LSASVGDRVT ITCRASQDIS SALVWYQQKP GKAPKLLIYD ASSLESGVPS
RFSGSESGTD FTLTISSLQP EDFATYYCQQ FNSYPLTFGG GTKVEIKRTV AAPSVFIFPP
SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT
LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC
(D chain)
DIQMTQSPSS VSASVGDRVT ITCRASQGIS NWLAWFQHKP GKAPKLLIYA ASSLLSGVPS
RFSGSGSGTD FTLTISSLQP EDFATYYCQQ ANSFPITFGQ GTRLEIKRTV AAPSVFIFPP
SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT
LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC
(Disulfide bridge: A22-A96, A152-A208, A228-C214, A234-B228, A237-B231, A269-A329, A375-A433, B22-B96, B146-B202, B222-D214, B263-B323, B369-B427, C23-C88, C134-C194, D23-D88, D134-D194)
Amivantamab
FDA APPR 2021/5/21 Rybrevant
アミバンタマブ (遺伝子組換え)
Formula |
C6472H10014N1730O2023S46
|
---|---|
CAS |
2171511-58-1
|
Mol weight |
145900.1288
|
- CNTO-4424
- JNJ 61186372
- JNJ-611
- JNJ-61186372
EfficacyDisease |
Antineoplastic
|
---|---|
Non-small cell lung cancer (EGFR exon 20 insertion)
|
|
Comment |
Monoclonal antibody
|
FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer
On May 21, 2021, the Food and Drug Administration granted accelerated approval to amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.), a bispecific antibody directed against epidermal growth factor (EGF) and MET receptors, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.
FDA also approved the Guardant360® CDx (Guardant Health, Inc.) as a companion diagnostic for amivantamab-vmjw.
Approval was based on CHRYSALIS, a multicenter, non-randomized, open label, multicohort clinical trial (NCT02609776) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Efficacy was evaluated in 81 patients with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. Patients received amivantamab-vmjw once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review (BICR) and response duration. The ORR was 40% (95% CI: 29%, 51%) with a median response duration of 11.1 months (95% CI: 6.9, not evaluable).
The most common adverse reactions (≥ 20%) were rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.
The recommended dose of amivantamab-vmjw is 1050 mg for patients with baseline body weight < 80 kg, and 1400 mg for those with body weight ≥ 80 kg, administered weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
View full prescribing information for Rybrevant.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency (ANVISA) and United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.
This product was granted breakthrough therapy designation for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Amivantamab, sold under the brand name Rybrevant, is a monoclonal antibody medication used to treat non-small cell lung cancer.[1][2][3]
The most common side effects include rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, swelling in the lower legs or hands or face, sores in the mouth, cough, constipation, vomiting and changes in certain blood tests.[2][3]
Amivantamab is a bispecific epidermal growth factor (EGF) receptor-directed and mesenchymal–epithelial transition (MET) receptor-directed antibody. It is the first treatment for adults with non-small cell lung cancer whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations.[2]
Amivantamab was approved for medical use in the United States in May 2021.[2][3][4][5]
Amivantamab, also known as JNJ-61186372, is an anti-EGFR-MET bispecific antibody, derived from Chinese hamster ovary cells, approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.1,9 Patients with NSCLC often develop resistance to drugs that target EGFR and MET individually, so amivantamab was developed to attack both targets, reducing the chance of resistance developing.1,2 Amivantamab was found to be more effective than the EGFR inhibitor erlotinib or the MET inhibitor crizotinib in vivo.1,3 Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and were generally treated with platinum-based therapy.5
Amivantamab was granted FDA approval on 21 May 2021.9
Medical uses
Amivantamab is indicated for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.[3]
History
The U.S. Food and Drug Administration (FDA) approved amivantamab based on CHRYSALIS, a multicenter, non-randomized, open label, multicohort clinical trial (NCT02609776) which included participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.[3] Efficacy was evaluated in 81 participants with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy.[3]
The FDA collaborated on the review of amivantamab with the Brazilian Health Regulatory Agency (ANVISA) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA).[3] The application reviews are ongoing at the other regulatory agencies.[3]
Society and culture
Legal status
Amivantamab was approved for medical use in the United States in May 2021.[2][3][4][5] A marketing authorization application is pending in the EU.[6][7]
Names
Amivantamab is the recommended international nonproprietary name (INN).[8]
Research
Amivantamab is being investigated in combination with lazertinib versus osimertinib; and in combination with carboplatin-pemetrexed chemotherapy compared to carboplatin-pemetrexed.[9][10]
PAPER
https://www.jbc.org/article/S0021-9258(21)00427-0/fulltext#secsectitle0085
Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET
Experimental procedures
Preparation of BsAb panel
The generation of parental antibodies followed expression and purification protocols as described (
,
). The MET parental mAbs had the F405L mutation and the EGFR parental mAbs had the K409R mutation. The IgG1 b12 arm served as isotype control and null arm to preserve the BsAb architecture. The low fucose parental mAbs were generated using proprietary cell lines. The quality of the BsAb were confirmed as being monodisperse and monomeric via size exclusion chromatography and being pure via SDS-PAGE.
Flow cytometric binding assay
MET phosphorylation assay
Proliferation assays
EGFR phosphorylation assay
Expression and purification of proteins for crystallization
Crystallization and structure determination
Epitope and paratope residues were assigned within a 4-Å contact distance cutoff using the CCP4 program CONTACT. The epitope area was calculated with the CCP4 program AREA. The buried surface area of binding residues was calculated with the program MOE (
). Structural overlays of equivalent Cα atoms in the Sema domain (residues 40–515; PDB codes 1SHY, 4K3J, 2UZX, and 2UZY) were performed with COOT. Molecular graphics were generated with PyMol (PyMOL Molecular Graphics System, Version 1.4.1, Schrödinger, LLC) and MOE. The atomic coordinates and structure factors for the amivantamab anti-MET Fab–MET Sema-PSI complex were deposited in the RCSB PDB (accession code 6WVZ).
HCC827-HGF xenograft model
References
- ^ Jump up to:a b “Rybrevant- amivantamab injection”. DailyMed. Janssen Pharmaceutical Companies. Retrieved 25 May 2021.
- ^ Jump up to:a b c d e f “FDA Approves First Targeted Therapy for Subset of Non-Small Cell Lung Cancer”. U.S. Food and Drug Administration (FDA) (Press release). 21 May 2021. Retrieved 21 May 2021.
This article incorporates text from this source, which is in the public domain.
- ^ Jump up to:a b c d e f g h i j “FDA grants accelerated approval to amivantamab-vmjw for mNSCLC”. U.S. Food and Drug Administration (FDA). 21 May 2021. Retrieved 21 May 2021.
This article incorporates text from this source, which is in the public domain.
- ^ Jump up to:a b “Rybrevant (amivantamab-vmjw) Receives FDA Approval as the First Targeted Treatment for Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations” (Press release). Janssen Pharmaceutical Companies. 21 May 2021. Retrieved 21 May 2021 – via PR Newswire.
- ^ Jump up to:a b “Genmab Announces that Janssen has been Granted U.S. FDA” (Press release). Genmab A/S. 21 May 2021. Retrieved 21 May 2021 – via GlobeNewswire.
- ^ “Amivantamab”. SPS – Specialist Pharmacy Service. 25 February 2021. Retrieved 23 May 2021.
- ^ “Janssen Submits European Marketing Authorisation Application for Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations” (Press release). Janssen Pharmaceutical Companies. 28 December 2020. Retrieved 23 May 2021 – via Business Wire.
- ^ World Health Organization (2020). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 83” (PDF). WHO Drug Information. 34 (1).
- ^ Kaplon H, Reichert JM (2021). “Antibodies to watch in 2021”. mAbs. 13 (1): 1860476. doi:10.1080/19420862.2020.1860476. PMC 7833761. PMID 33459118.
- ^ “Updated Amivantamab and Lazertinib Combination Data Demonstrate Durable Responses and Clinical Activity for Osimertinib-Relapsed Patients with EGFR-Mutated Non-Small Cell Lung Cancer” (Press release). Janssen Pharmaceutical Companies. 20 May 2021. Retrieved 23 May 2021 – via Business Wire.
Further reading
- Neijssen J, Cardoso RM, Chevalier KM, Wiegman L, Valerius T, Anderson GM, et al. (April 2021). “Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET”. J Biol Chem. 296: 100641. doi:10.1016/j.jbc.2021.100641. PMC 8113745. PMID 33839159.
- Yun J, Lee SH, Kim SY, Jeong SY, Kim JH, Pyo KH, et al. (August 2020). “Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC”. Cancer Discov. 10 (8): 1194–1209. doi:10.1158/2159-8290.CD-20-0116. PMID 32414908.
External links
- “Amivantamab”. Drug Information Portal. U.S. National Library of Medicine.
- Clinical trial number NCT02609776 for “Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS)” at ClinicalTrials.gov
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Human |
Target | Epidermal growth factor receptor (EGFR) and Mesenchymal–epithelial transition (MET) |
Clinical data | |
Trade names | Rybrevant |
Other names | JNJ-61186372, amivantamab-vmjw |
License data |
|
Routes of administration |
Intravenous infusion |
Drug class | Antineoplastic |
ATC code |
|
Legal status | |
Legal status | |
Identifiers | |
CAS Number |
|
DrugBank | |
UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6472H10014N1730O2023S46 |
Molar mass | 145902.15 g·mol−1 |
NAME | DOSAGE | STRENGTH | ROUTE | LABELLER | MARKETING START | MARKETING END | ||
---|---|---|---|---|---|---|---|---|
Rybrevant | Injection | 350 mg/1 | Intravenous | Janssen Biotech, Inc. | 2021-05-21 | Not applicable |
/////////Amivantamab, FDA 2021, APPROVALS 2021, PEPTIDE, Rybrevant, アミバンタマブ (遺伝子組換え), CNTO-4424, JNJ 61186372, JNJ-611, JNJ-61186372, breakthrough therapy designation, Janssen Biotech