Disitamab vedotin

Summary

Disitamab vedotin (RC48) is an anti-HER2 antibody-drug conjugate developed by RemeGen. It is approved in China for HER2-positive gastric/gastroesophageal junction cancer and HER2-positive urothelial carcinoma. It is under investigation in multiple global clinical trials for various HER2-expressing solid tumors.

Mechanism of Action

Disitamab vedotin is an anti-HER2 antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 IgG1 monoclonal antibody (disitamab) conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable linker. Upon binding to HER2-expressing tumor cells, the ADC is internalized, the linker is cleaved, and MMAE is released intracellularly, inhibiting microtubule polymerization and inducing cell cycle arrest and apoptosis.

Routes of Administration

Goals & Uses

• Treatment of other HER2-expressing solid tumorsOncologyLow
• Treatment of HER2-expressing breast cancerOncologyModerate
• Treatment of HER2-positive urothelial carcinomaOncologyHigh
• Treatment of HER2-overexpressing gastric/gastroesophageal junction adenocarcinomaOncologyHigh

Contraindications

• Hypersensitivity to disitamab vedotin or any componentAllergy/ImmunologyHigh
• Severe hepatic impairmentOrganModerateLiver function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data

Adverse Effects

• Peripheral neuropathyNeurologicalCommon
• Elevated liver enzymes (AST/ALT)HepatotoxicityCommon
• AlopeciaDermatologicCommonHair loss
• Nausea/vomitingGastrointestinalCommon
• Infusion-related reactionsHypersensitivityUncommon
• Myelosuppression (neutropenia, anemia, thrombocytopenia)HematologicalCommon

Drug Interactions

• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
• P-glycoprotein (P-gp) inhibitorsModerate
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)High

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveAbsolute
• Patients with pre-existing peripheral neuropathyNeurologicalRelative
• Patients with severe hepatic impairmentHepaticRelative
• Pregnant womenReproductiveAbsolute

Regulatory Status

• CNApprovedApproved: HER2-overexpressing (IHC 2+ or 3+) locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two systemic therapies, HER2-positive (IHC 2+ or 3+) locally advanced or metastatic urothelial carcinomaApproved by NMPA (National Medical Products Administration) in June 2021 (gastric cancer) and 2023 (urothelial carcinoma).
• European UnionInvestigationalUnder clinical investigation; not approved by EMA as of current data.
• United StatesInvestigationalFDA Breakthrough Therapy designation granted for HER2-positive urothelial carcinoma. Active Phase II/III clinical trials ongoing. Not yet FDA approved.

Approved by the National Medical Products Administration (NMPA) of China in 2021 for HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma, and in 2023 for HER2-positive locally advanced or metastatic urothelial carcinoma. Under FDA Breakthrough Therapy designation and active Phase II/III trials in the US and globally.

Evidence & Sources

No sources recorded yet.