Amivantamab Continues to Deliver Positive Clinical and Regulatory Updates as the Leading EGFR×c-MET Bispecific Antibody

Oct 11, 2023 21:13 CST Updated 21:13

Johnson & Johnson

Medical Device R&D and Manufacturer

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On September 28, 2023, Johnson & Johnson announced RYBREVANT (amivantamab) in combination with Lazertinib head-to-head against Osimertinib（osimertinib）The MARIPOSA study for first-line treatment of EGFR+ NSCLC met the primary endpoint of statistically and clinically significant PFS. Meanwhile,Compared with Osimertinib,Amivantamab+Lazertinib showed a trend of overall survival (OS) benefit.

Meanwhile, on October 6, 2023, Janssen Pharmaceutical Companies announced the submission of a Type II variation application to the European Medicines Agency (EMA) for the approval of RYBREVANT (amivantamab) in combination with chemotherapy (carboplatin and pemetrexed) as a first-line treatment for adult patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.

AmivantamabIt is currently the only approved and marketed EGFRxc-MET bispecific antibody. The affinity of the EGFR antibody end is lower than that of the c-MET antibody. However, the affinity design of Merus' 1+1 asymmetric EGFRxc-MET bispecific antibody does not have this characteristic.AmivantamabThe difference between the two is not significant.

Some current views suggest that differences in affinity have led to current clinical variations, and EGFRxc-MET bispecific antibodies with a 2+2 symmetric design have not been able to adequately modulate affinity.

AZ adopted Johnson & Johnson's design approach in the development of EGFRxc-MET bispecific antibody ADC. I mentioned in "What Are the Implications of AstraZeneca's Bispecific Antibody (EGFRxcMET) ADC?"It was elaborated in detail in the article." In other words, nowadays, the consideration of bispecific antibodies cannot simply be that putting two antibodies together can result in a viable drug.

At the same time, the druggability of EGFRxc-MET bispecific antibodies does not necessarily mean that all EGFRxc-MET bispecific antibody ADCs can be druggable. The mechanisms are different, and the dosages are also different.EGFRxc-MET bispecific antibody is more aboutThe biological function of the target itself, as well as the ADCC effect mediated by the antibody, andEGFRxc-MET Bispecific AntibodyADCs are more about targeted delivery of chemical drugs into tumor cells. Based on current experience,After ADC is conjugated with small molecule toxins via thiol or sugar, its ADCC will be somewhat weakened. This explains why DS8201, despite having a dosage similar to trastuzumab, does not cause myocarditis in the same way as trastuzumab.

ButThe Design of AmivantamabIn the future application of bispecific antibody-drug conjugates (ADCs), a good reference is clearly provided, including for some targets with relatively severe on-target toxicity, such as TROP2. Such targets might be able to avoid on-target toxicity through this kind of design.

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