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Disitamab vedotin, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpression and HER2-low advanced breast cancer: a phase I/Ib study.
- Source :
-
Cancer communications (London, England) [Cancer Commun (Lond)] 2024 Jul; Vol. 44 (7), pp. 833-851. Date of Electronic Publication: 2024 Jun 28. - Publication Year :
- 2024
-
Abstract
- Background: Disitamab vedotin (DV; RC48-ADC) is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2 (HER2)-directed antibody, linker and monomethyl auristatin E. Preclinical studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast, gastric, and ovarian cancers with different levels of HER2 expression. In this pooled analysis, we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer (ABC).<br />Methods: In the phase I dose-escalation study (C001 CANCER), HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks (Q2W) until unacceptable toxicity or progressive disease. The dose range, safety, and pharmacokinetics (PK) were determined. The phase Ib dose-range and expansion study (C003 CANCER) enrolled two cohorts: HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W, with the recommended phase 2 dose (RP2D) determined, and HER2-low ABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ABC.<br />Results: Twenty-four patients with HER2-overexpression ABC in C001 CANCER, 46 patients with HER2-overexpression ABC and 66 patients with HER2-low ABC in C003 CANCER were enrolled. At 2.0 mg/kg RP2D Q2W, the confirmed objective response rates were 42.9% (9/21; 95% confidence interval [CI]: 21.8%-66.0%) and 33.3% (22/66; 95% CI: 22.2%-46.0%), with median progression-free survival (PFS) of 5.7 months (95% CI: 5.3-8.4 months) and 5.1 months (95% CI: 4.1-6.6 months) for HER2-overexpression and HER2-low ABC, respectively. Common (≥5%) grade 3 or higher treatment-emergent adverse events included neutrophil count decreased (17.6%), gamma-glutamyl transferase increased (13.2%), asthenia (11.0%), white blood cell count decreased (9.6%), peripheral neuropathy such as hypoesthesia (5.9%) and neurotoxicity (0.7%), and pain (5.9%).<br />Conclusion: DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC, with a favorable safety profile at 2.0 mg/kg Q2W.<br /> (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)
- Subjects :
- Humans
Female
Middle Aged
Aged
Adult
Aged, 80 and over
Receptor, ErbB-2 metabolism
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Breast Neoplasms metabolism
Immunoconjugates administration & dosage
Immunoconjugates therapeutic use
Immunoconjugates pharmacokinetics
Immunoconjugates adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 2523-3548
- Volume :
- 44
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer communications (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 38940019
- Full Text :
- https://doi.org/10.1002/cac2.12577