Antibody-drug conjugate containing a heterocyclic compound that has an inducing effect on the degradation of the mutant kras protein

Abstract

An antibody-drug conjugate is provided for use in the treatment of cancer expressing mutant KRAS, in particular, mutant KRAS G12V, mutant G12D, and mutant G12C. A drug and a drug-linker conjugate for use in the antibody-drug conjugate are also provided. The present inventors have conjugated a heterocyclic compound that induces the degradation of mutant KRAS protein, wherein the heterocyclic compound is represented by formula (II), with an anti-EGFR antibody to prepare an antibody-drug conjugate capable of delivering the compound to a type of cancer that expresses EGFR. Furthermore, a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof has been found.The antibody-drug conjugate inhibits mutant KRAS by inducing the degradation of mutant KRAS, in particular, mutant KRAS protein G12V, mutant G12D and mutant G12C, in a type of cancer that expresses EGFR, and exhibits an antitumor effect.