Zolbetuximab Plus mFOLFOX6 Trial Overview

The final analysis was planned when 300 patients had disease progression or died.

The assumed median progression-free survival was 9 months for zolbetuximab plus mFOLFOX6 versus 6 months for placebo plus mFOLFOX6.

The overall one-sided significance level used was 0.025.

<p>A 10% dropout rate was considered in the sample size calculation.</p> Signup and view all the answers

<p>There were 25 adverse events in one group and 12 in the other group.</p> Signup and view all the answers

<p>The hazard ratio is 0·75.</p> Signup and view all the answers

<p>87% of patients in the zolbetuximab group experienced grade 3 or worse adverse events.</p> Signup and view all the answers

<p>Nausea and vomiting are two of the most common all-grade adverse events.</p> Signup and view all the answers

<p>There were five treatment-related deaths in the zolbetuximab group.</p> Signup and view all the answers

<p>It significantly prolonged progression-free survival and overall survival.</p> Signup and view all the answers

<p>It might be a new first-line treatment for CLDN18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma.</p> Signup and view all the answers

<p>The confidence interval is 95% CI 0·60–0·94, indicating a statistically significant result.</p> Signup and view all the answers

<p>The combination significantly prolonged survival compared to placebo plus mFOLFOX6.</p> Signup and view all the answers

<p>The primary endpoint was progression-free survival per RECIST version 1.1, and key secondary endpoints included overall survival and time to confirmed deterioration.</p> Signup and view all the answers

<p>Health-related quality-of-life assessments were conducted at screening, every 3 weeks during treatment, and at treatment discontinuation, 30 days, and 90 days after discontinuation.</p> Signup and view all the answers

<p>Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.</p> Signup and view all the answers

<p>RECIST stands for Response Evaluation Criteria in Solid Tumors, and it is important for assessing objective response and duration of response in patients with measurable lesions.</p> Signup and view all the answers

<p>Additional patient-reported outcomes included measures from the QLQ-C30, QLQ-OG25, Global Pain, and EuroQOL Five-Dimensions Questionnaire.</p> Signup and view all the answers

<p>Progression-free survival per RECIST version 1.1 was determined by an independent review committee.</p> Signup and view all the answers

<p>Adverse events were monitored throughout the trial and for 90 days after treatment discontinuation.</p> Signup and view all the answers

<p>Objective response was assessed as an ad-hoc analysis in patients with measurable lesions.</p> Signup and view all the answers

<p>NCT03504397</p> Signup and view all the answers

<p>77%</p> Signup and view all the answers

<p>The funder was involved in study design, data collection, analysis, interpretation, and report writing.</p> Signup and view all the answers

<p>Diffuse classification with 41%.</p> Signup and view all the answers

<p>2735 patients.</p> Signup and view all the answers

<p>Approximately 51 months.</p> Signup and view all the answers

<p>13%.</p> Signup and view all the answers

<p>It includes all randomized patients who received at least one dose of any study drug.</p> Signup and view all the answers

<p>62 patients.</p> Signup and view all the answers

<p>East version 6.4 for sample size calculations and SAS version 9.3 or later for statistical analyses.</p> Signup and view all the answers

<p>30%.</p> Signup and view all the answers

<p>Patients with metastases classified as having 0-2 tumors.</p> Signup and view all the answers

<p>80% in the first group and 76% in the second group.</p> Signup and view all the answers

<p>The placebo group's median progression-free survival was 6.4 months compared to the zolbetuximab group's longer duration.</p> Signup and view all the answers

<p>The rate was 87% in the zolbetuximab group.</p> Signup and view all the answers

<p>Nausea led to discontinuation in 6% of patients and vomiting led to discontinuation in 7% of patients in the zolbetuximab group.</p> Signup and view all the answers

<p>Females showed a 23.75% incidence compared to 17.38% in males.</p> Signup and view all the answers

<p>The rate in Asia was 21.49% compared to 16.99% in non-Asia.</p> Signup and view all the answers

<p>Patients with previous gastrectomy had a higher incidence of 24.80% compared to 16.95% in those without.</p> Signup and view all the answers

<p>20.24% of patients with stomach cancer experienced adverse events.</p> Signup and view all the answers

<p>Patients with 0-2 metastatic sites had a 19.68% rate of adverse events.</p> Signup and view all the answers

<p>Asian patients had a higher rate of 23.33% compared to 16.13% in White patients.</p> Signup and view all the answers

<p>Never smokers had an 18.96% event rate while former smokers had 17.81%.</p> Signup and view all the answers

<p>The zolbetuximab plus mFOLFOX6 group appeared more favorable.</p> Signup and view all the answers

<p>Combining zolbetuximab with mFOLFOX6 led to improved patient outcomes compared to placebo.</p> Signup and view all the answers

<p>The text does not specify any treatment-related deaths in the zolbetuximab group.</p> Signup and view all the answers

<p>Patients were randomly assigned via block randomisation with a 1:1 ratio.</p> Signup and view all the answers

<p>Patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma were targeted.</p> Signup and view all the answers

<p>Zolbetuximab and placebo were identical in appearance and were administered by unmasked pharmacists.</p> Signup and view all the answers

<p>The regimen started with 800 mg/m² on cycle 1, day 1, followed by 600 mg/m² on cycle 1, day 22, and days 1 and 22 of subsequent cycles.</p> Signup and view all the answers

<p>Stratification focused on region (Asia vs non-Asia), number of metastases, and previous gastrectomy status.</p> Signup and view all the answers

<p>It explored a new treatment combination that showed improved survival in advanced gastric or gastro-oesophageal junction adenocarcinoma.</p> Signup and view all the answers

<p>The trial was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki.</p> Signup and view all the answers

<p>Double-blind indicates that both participants and investigators were unaware of which treatment group the patients were assigned to.</p> Signup and view all the answers

<p>Gastric and gastro-oesophageal junction adenocarcinomas.</p> Signup and view all the answers

<p>Platinum-fluoropyrimidine chemotherapy, including mFOLFOX6.</p> Signup and view all the answers

<p>It is approved for combination with chemotherapy in patients with HER2-positive disease.</p> Signup and view all the answers

<p>There is an unmet need for additional targeted therapies to prolong survival.</p> Signup and view all the answers

<p>Non-immunotherapy, biomarker-based therapies.</p> Signup and view all the answers

<p>It indicates greater efficacy of checkpoint inhibition therapies like nivolumab in eligible patients.</p> Signup and view all the answers

<p>Zolbetuximab and mFOLFOX6.</p> Signup and view all the answers

<p>It aims to improve progression-free survival and overall survival compared to placebo.</p> Signup and view all the answers

<p>Improved patient outcomes in specific gastric cancer populations.</p> Signup and view all the answers

<p>It notes the highest incidence rates in Asia, Latin America, and eastern Europe.</p> Signup and view all the answers

<p>≥75%</p> Signup and view all the answers

<p>Four cycles.</p> Signup and view all the answers

<p>Imaging assessed according to RECIST version 1.1.</p> Signup and view all the answers

<p>To assess patient performance status.</p> Signup and view all the answers

<p>400 mg/m² (folinic acid) or 200 mg/m² (levofolinate).</p> Signup and view all the answers

<p>It showed prolonged survival in patients with advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.</p> Signup and view all the answers

<p>HER2-negative and CLDN18.2-positive tumors.</p> Signup and view all the answers

<p>The Ovid Embase database was searched and filtered by time restrictions and articles related to CLDN18.2 positivity.</p> Signup and view all the answers

<p>Nausea and vomiting were the main adverse effects that frequently caused discontinuation.</p> Signup and view all the answers

<p>Until disease progression, toxic effects, or start of another anticancer treatment.</p> Signup and view all the answers

<p>VENTANA CLDN18 [43-14A] RxDx Assay.</p> Signup and view all the answers

<p>The safety profile was deemed manageable, although adverse events were more frequent in the zolbetuximab group.</p> Signup and view all the answers

<p>Nearly 40% of screened patients had tumors that met the definition of CLDN18.2 positivity used in the study.</p> Signup and view all the answers

<p>The primary focus is on advanced unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.</p> Signup and view all the answers

<p>The studies primarily belonged to phase 2 and phase 3 clinical trials.</p> Signup and view all the answers

<p>Adverse events were monitored post-discontinuation to assess any late-emerging safety concerns.</p> Signup and view all the answers

<p>HR of 0.80</p> Signup and view all the answers

<p>Only after rejection of the hypothesis for progression-free survival.</p> Signup and view all the answers

<p>0.025</p> Signup and view all the answers

<p>Withdrawal by patient, laboratory findings, HER2 expression status, or ECOG performance status score.</p> Signup and view all the answers

<p>396 deaths</p> Signup and view all the answers

<p>It allowed for early assessment of overall survival based on initial results.</p> Signup and view all the answers

<p>Summarized as individual reasons leading to a higher total than actual discontinuations.</p> Signup and view all the answers

<p>To evaluate the treatment's impact on patients' overall well-being.</p> Signup and view all the answers

<p>The distribution could skew survival outcomes, suggesting that demographic factors might affect treatment efficacy.</p> Signup and view all the answers

<p>It delayed the separation of survival curves, complicating comparisons of treatment efficacy between groups.</p> Signup and view all the answers

<p>Subgroup analyses help identify if certain populations respond differently to treatment, affecting tailored therapeutic approaches.</p> Signup and view all the answers

<p>It suggests that the treatment might not meet the expected efficacy benchmarks, raising questions about its effectiveness.</p> Signup and view all the answers

<p>Long-term follow-up helps to assess durability of treatment effects and long-term safety, informing future therapeutic strategies.</p> Signup and view all the answers