Related Reading:
1）《cMet/EGFR Bispecific Antibody Amivantamab Screening Strategy》
2）《Johnson & Johnson's EGFR/cMET Bispecific Antibody Amivantamab Approved for Marketing》
3）《"The New King" Takes the Throne!》
Johnson & Johnson's Amivantamab was approved for marketing by the FDA on May 21, 2021, for the treatment of non-small cell lung cancer with EGFR exon 20 insertion mutations. The drug was submitted for marketing approval in December 2020 based on phase I clinical data.On August 20, 2024, Johnson & Johnson announced that the combination therapy of amivantamab + lazertinib successfully defeatedOsimertinib becomesEGFR Mutation (Deletion in exon 19 or L858R substitution mutation in exon 21) Advanced lung cancer patientsFirst-line chemotherapy-free treatment option for patients approved by the FDA。The success of amivantamab has solidified Johnson & Johnson's position in the lung cancer field, while the subsequent development of bispecific antibody-drug conjugates (ADCs) has also brought pressure to Johnson & Johnson. However, Johnson & Johnson did not sit idly by.Recently, Johnson & Johnson presented its EGFR/cMET-bispecific ADC at AACR.JNJ-95437446ThePreclinical data.JNJ-95437446 utilizes the bismaleimide linker-payload CPT-113 provided by Hangzhou Dox BioTech Co., Ltd. to maintain antibody stability post-conjugation and deliver the topoisomerase I inhibitor into tumor cells. Preclinical studies have shown that JNJ-95437446 retains EGFR and MET binding capabilities similar to amivantamab, induces rapid internalization, and exhibits potent, target-dependent cytotoxicity in vitro. Additionally, the payload released by this antibody-drug conjugate demonstrates a bystander cytotoxic effect. In preclinical xenograft models of non-small cell lung cancer (NSCLC) derived from cell lines, including lung adenocarcinoma and squamous cell carcinoma, as well as in models resistant to amivantamab, JNJ-95437446 has demonstrated robust anti-tumor activity, achieving complete tumor regression in some cases. In multi-dose GLP safety assessment studies in non-human primates, JNJ-95437446 showed good tolerability, with pharmacokinetic analyses confirming excellent linker/payload stability.
In terms of integration,JNJ-95437446 conjugated with the toxin did not affect its binding ability, which remained similar to the binding ability of the previous antibody.
For the development of ADC, antibody internalization is an important property,Amivantamab was not specifically optimized for internalization during its initial screening, but the conjugated antibody still demonstrates relatively good internalization efficiency.In terms of in vitro activity,JNJ-95437446 can effectively inhibit EGFR-amplified HCC827 tumor cells.
In cell line-derived xenograft models and patient-derived xenograft models of non-small cell lung cancer with various driver gene mutations (including mutation types known to cause resistance to amivantamab), JNJ-95437446 demonstrated significant single-dose in vivo anti-tumor activity.
Summary
Johnson & Johnson's precise design of the antibody for Amivantamab in the clinicalBedexhibited excellence inThe clinical efficacy has broken through the field of lung cancer and expanded to head and neck cancer andColorectal Cancer.The success of Amivantamab has also promoted the development of related ADCs, with more than 10 EGFR/cMET bispecific antibody ADCs currently in development and entering clinical trials.Amivantamab's original developer, Genmab, recently discontinuedEGFR x cMET Bispecific Antibody ADCThe development of GEN1268 has also cast a shadow over the development of ADCs in this field.EGFR/cMET Bispecific Antibody ADC Halts Clinical Development?》。The tweet is used to convey knowledge. If you have any questions about copyright, etc., please contact PharmaExpress within 30 days of the publication of this article.Original content cannot be reproduced on other platforms without authorization.©2021 PharmaExpress. All rights reserved.
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