Disitamab vedotin
Also known as: Aidixi, Disitamab vedotin, HER2‑ADC, RC48, RC48-ADC, 爱地希
Source Disitamab vedotin at Peptiology
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Summary
Disitamab vedotin (Aidixi®, RC48) is an antibody‑drug conjugate that targets the human epidermal growth factor receptor 2 (HER2). It is approved in China for HER2‑positive locally advanced or metastatic gastric cancer and is being investigated in other HER2‑expressing solid tumours, including breast, urothelial and biliary tract cancers. The drug consists of a HER2‑directed monoclonal antibody linked to the cytotoxic payload monomethyl auristatin E, and is administered intravenously on a bi‑weekly schedule.
Mechanism of Action
The monoclonal antibody component of disitamab vedotin binds to extracellular domains of HER2 on tumour cells. Upon binding, the complex is internalised and trafficked to lysosomes, where a cleavable linker is enzymatically broken, releasing monomethyl auristatin E. MMAE binds tubulin, disrupting microtubule assembly, arresting mitosis and triggering apoptotic cell death. Selective delivery to HER2‑expressing cells concentrates the cytotoxic effect while sparing most normal tissues.
What the Research Shows
Pre‑clinical work showed potent activity against HER2‑positive breast, gastric and ovarian models. The first regulatory approval (June 2021, China) was for HER2‑overexpressing gastric cancer after two prior chemotherapy lines. A phase I/Ib breast cancer study reported objective response rates of 42.9% in HER2‑overexpressing and 33.3% in HER2‑low disease at the recommended 2 mg/kg dose, with median progression‑free survival of about 5 months. In urothelial carcinoma, a phase Ib/II trial of disitamab vedotin plus the PD‑1 inhibitor toripalimab yielded a 73% confirmed response and median PFS of 9.3 months. A subsequent phase III trial demonstrated that the combination significantly prolonged PFS (13.1 vs 6.5 months) and overall survival (31.5 vs 16.9 months) compared with chemotherapy, with an objective response of 76% versus 50%. A combined analysis of two phase II urothelial studies confirmed activity and a manageable safety profile.
Reported Benefits
Disitamab vedotin is an approved therapy for HER2‑positive gastric cancer, providing a targeted option after standard chemotherapy. Early‑phase trials show activity in HER2‑overexpressing and HER2‑low breast cancer, achieving response rates above 30%. In urothelial carcinoma, especially when combined with toripalimab, the drug produces high response rates (up to 76%) and extends progression‑free and overall survival relative to chemotherapy. The antibody‑drug conjugate format delivers the potent MMAE payload selectively to HER2‑positive cells, potentially improving efficacy while limiting systemic toxicity.
Limitations of the Evidence
Evidence is largely derived from early‑phase studies and trials conducted primarily in Chinese populations; broader geographic validation is limited. In breast cancer, response rates in HER2‑low disease are modest and durability data are sparse. Long‑term safety beyond the reported follow‑up periods remains unclear. Comparative data versus other HER2‑targeted ADCs are limited, and ongoing phase III trials are needed to confirm superiority. HER2 testing standards for non‑breast/non‑gastric tumours, such as NSCLC, are still evolving.
Safety Considerations
Common grade ≥ 3 adverse events include neutropenia (≈ 18%), elevated liver enzymes (γ‑glutamyltransferase, ALT/AST), asthenia, and peripheral sensory neuropathy. Hepatic toxicity was frequent when combined with toripalimab, and one treatment‑related death from pneumonitis was reported. Peripheral neuropathy can be dose‑limiting. Overall, the safety profile is considered manageable, but patients require regular monitoring of blood counts, liver function and neurological status, with dose adjustments as needed.
How It Is Administered
Disitamab vedotin is administered intravenously every two weeks. Dose‑finding studies evaluated 0.5–2.5 mg/kg; the recommended phase 2 dose as monotherapy is 2 mg/kg. In combination regimens, the antibody‑drug conjugate is given at 2 mg/kg together with toripalimab 3 mg/kg, both on a bi‑weekly schedule. The drug is supplied as a sterile solution for infusion.
Routes of Administration
Goals & Uses
- Treatment of other HER2-expressing solid tumorsOncologyLow
- Treatment of HER2-expressing breast cancerOncologyModerate
- Treatment of HER2-positive urothelial carcinomaOncologyHigh
- HER2‑positive gastric cancerOncologyHigh
- HER2‑positive colorectal cancerOncologyModerate
- Treatment of HER2-overexpressing gastric/gastroesophageal junction adenocarcinomaOncologyHigh
- HER2‑positive breast cancerOncologyModerate
Contraindications
- Hypersensitivity to disitamab vedotin or any componentAllergy/ImmunologyHigh
- Severe hepatic impairment (Child‑Pugh C)Liver DiseaseModerate
- Severe hepatic impairmentOrganModerateLiver function concerns
- Known hypersensitivity to Disitamab vedotin or MMAEAllergyHigh
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
Adverse Effects
- Peripheral neuropathyNeurologicalCommon
- Elevated liver enzymes (AST/ALT)HepatotoxicityCommon
- AlopeciaDermatologicCommonHair loss
- Nausea/vomitingGastrointestinalCommon
- Infusion‑related reactionsGeneralCommon
- NeutropeniaHematologicCommonLow neutrophil count
- FatigueGeneralCommonLow energy or tiredness
- Infusion-related reactionsHypersensitivityUncommon
- Myelosuppression (neutropenia, anemia, thrombocytopenia)HematologicalCommon
Drug Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine)Moderate
- Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
- P-glycoprotein (P-gp) inhibitorsModerate
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)Moderate
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)High
- Anticoagulants (e.g., warfarin, DOACs)Low
Population Constraints
- PregnancyReproductive SafetyAbsolute
- Pediatric patientsAgeRelative
- Breastfeeding womenReproductiveAbsolute
- Pediatric patients (<18 y)AgeRelative
- LactationReproductiveRelative
- 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 EMA review; clinical studies ongoing.
- United StatesInvestigationalPhase II/III trials for HER2‑positive gastric and breast cancers.
- United KingdomInvestigationalMHRA has granted clinical trial authorization.
Approved by the National Medical Products Administration (NMPA, China) in 2021. Not yet approved in the US, EU, or UK; currently in Phase II/III trials in those regions.
Evidence & Sources
- Journal ArticleModerateWang J, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateDeeks ED2021-01-01T00:00:00.000000Z
- Journal ArticleModerateZhou L, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleModerateSheng X, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleModerateRen S, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateSheng X, et al.2024-01-01T00:00:00.000000Z
Frequently Asked Questions
What cancers is disitamab vedotin currently approved to treat?
It has received regulatory approval in China for HER2‑positive locally advanced or metastatic gastric cancer after at least two prior chemotherapy regimens. Other indications, such as breast or urothelial carcinoma, are still under clinical investigation.
How does the drug reach cancer cells while sparing normal tissue?
The monoclonal antibody component binds specifically to HER2 on tumour cells. After internalisation, a cleavable linker releases the cytotoxic MMAE inside the cell, concentrating the toxic effect where HER2 is expressed and reducing exposure to HER2‑negative tissues.
What are the most common serious side effects?
Serious (grade 3 or higher) toxicities reported include neutropenia, elevated liver enzymes (γ‑GT, ALT, AST), fatigue, and peripheral sensory neuropathy. When combined with the PD‑1 inhibitor toripalimab, hepatic toxicity is more frequent, and rare immune‑related events such as pneumonitis have occurred.
Can disitamab vedotin be used together with other cancer therapies?
Clinical trials have evaluated it in combination with the PD‑1 inhibitor toripalimab, showing high response rates and survival benefits in urothelial carcinoma. Ongoing studies are exploring other combinations, but co‑administration should be done only under clinical trial protocols or physician guidance.
What is Disitamab vedotin?
Disitamab vedotin (Aidixi®, RC48) is an antibody‑drug conjugate that targets the human epidermal growth factor receptor 2 (HER2). It is approved in China for HER2‑positive locally advanced or metastatic gastric cancer and is being investigated in other HER2‑expressing solid tumours, including breast, urothelial and biliary tract cancers. The drug consists of a HER2‑directed monoclonal antibody linked to the cytotoxic payload monomethyl auristatin E, and is administered intravenously on a bi‑weekly schedule.
What is Disitamab vedotin used for?
Disitamab vedotin is educationally associated with: Treatment of other HER2-expressing solid tumors, Treatment of HER2-expressing breast cancer, Treatment of HER2-positive urothelial carcinoma, HER2‑positive gastric cancer, HER2‑positive colorectal cancer, Treatment of HER2-overexpressing gastric/gastroesophageal junction adenocarcinoma, HER2‑positive breast cancer. Educational only — not medical advice.
How is Disitamab vedotin administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Disitamab vedotin?
Reported adverse effects include: Peripheral neuropathy, Elevated liver enzymes (AST/ALT), Alopecia, Nausea/vomiting, Infusion‑related reactions, Neutropenia, Fatigue, Infusion-related reactions, Myelosuppression (neutropenia, anemia, thrombocytopenia). This list is not exhaustive — consult a qualified clinician.
Who should avoid Disitamab vedotin?
Recorded contraindications: Hypersensitivity to disitamab vedotin or any component, Severe hepatic impairment (Child‑Pugh C), Severe hepatic impairment, Known hypersensitivity to Disitamab vedotin or MMAE, Pregnancy. Consult a qualified clinician before use.