Depatux-M combined temequinathemide therapy EGFR amplification relapse GBM

BackgroundedDepatux-M is a tumor-specific antibody drug coupling consisting of activated epithelial growth factor receptor (EGFR) antibodies (ABT-806) and toxin monomethylauristatin-FMartin van den Bent of the Brain Oncology Center of the Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and others conducted a randomized controlled Phase II trial of INTELLANCE 2 to study the efficacy of Depatux-M single-drug and combined pyroquine in the treatment of EGFR amplification recurrent glioblastoma (GBM)The results suggest that combination therapy may be effective for eGFR amplification GBM, which failed with standard therapies, and the paper was published online in Neuro-Oncol in November 2019research methodsepidermal growth factor receptor (EGFR) signaling abnormality played a prominent role in the pathogenesis of glioblastoma, but previous trials using EGFR inhibitors and antibodies failed to improve the prognosis of GBM patientsAntibody drug conjugate (ADC) is a new drug that targets extracellular cancer cells by binding to receptors and releasing cytotoxic substances such as qutobeumono or vibutuxireIn vitro studies confirmed that in the U87MG model expressed with EGFRvIII, antitumor activity increased when radiotherapy was combined with Depatux-M, and that Depatux-M combined with tamoxamine was more effective than combined radiotherapyINTELLANCE 2/EORTC 1410 is a multi-center, three-group comparison, randomized and open-label clinical Phase II trial with overall survival (Overall Survival, OS) as the main indicator of the outcomeThe researchers compared the anti-tumor efficacy of (1) Depatux-M combined with tamamine treatment; (2) Depatux-M single-drug therapy; and (3) the anti-tumor efficacy of three groups of patients treated with tebiomine or lomoxinIn patients with the first recurrence of EGFR amplification glioblastoma more than 3 months after chemotherapy for radiotherapy and tamoxetine at the age of 18 yearsExclude those who have previously been treated with nitrosaphy, bevazumab or EGFR target drugRandomly assigned patients were treated (1) Depatux-M 1.25 mg/kg (intravenous administration every 2 weeks) combined with tamamine (150-200 mg/m2, 1 cycle for 28 days, 1-5 days) respectively;findings260 patients were admitted between 10 March 2015 and 22 July 2016Among them, Depatux-M combined with tamamine treatment group 88 cases, Depatux-M single-drug treatment group 86 cases, control group 86 cases (Lomostin 61 cases and 25 cases of tamoxamine)No significant imbalance was observed in the patient's baseline characteristics Analysis in September 2017 found that 199 subjects died The main efficacy analysis at 15.0 months of median follow-up showed that the combined treatment group compared to the control group, HR was 0.71; The efficacy of Depatux-M monotherapy was compared to the control group, with HR: 1.04; The most common toxicity in patients treated with Depatux-M is reversible corneal epithelial lesions; The median follow-up time was 28.7 months, compared with the combined treatment group, HR: 0.66; In addition, in the patient group of patients with recurrence more than 16 weeks after the end of the treatment of temequina, the 2-year survival rate of patients in the combined therapy group was 28.6%, 95% CI, 13.5-45.6, and the 2-year survival rate of patients in the Depatux-M single-drug treatment group was 11.1%, 95% CI, 2.8-25.9; conclusions the authors note that the study is the first control trial of the "antibody drug conjugal" treatment of glioblastoma, and is specifically for the treatment of EGFR amplification glioblastoma Results show edgouts show that Depatux-M combined with pyremine therapy can improve the clinical efficacy of relapsed EGFR amplification glioblastoma, especially in patients with recurrence more than 16 weeks after the start of the last cycle of temolyne At the same time, it is proposed that the therapeutic effect of glioblastoma should continue to be explored for target EGFR receptors and other ADCs with better safety.