A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations

Overview

This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.

Full Title of Study: “A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 28, 2022

Interventions

  • Drug: Trastuzumab deruxtecan
    • Trastuzumab deruxtecan (T-DXd) by intravenous infusion

Arms, Groups and Cohorts

  • Experimental: T-DXd
    • T-DXd monotherapy

Clinical Trial Outcome Measures

Primary Measures

  • Confirmed objective response rate by RECIST 1.1 based on independent central review (ICR).
    • Time Frame: An average of approximately 12 months.
    • Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on ICR.

Secondary Measures

  • Duration of response (DoR) based on ICR assessment.
    • Time Frame: An average of approximately 12 months.
    • DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on ICR assessment.
  • Disease control rate (DCR) based on ICR assessment.
    • Time Frame: An average of approximately 12 months.
    • DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on ICR assessment.
  • Progression free survival (PFS) based on ICR assessment.
    • Time Frame: An average of approximately 12 months.
    • PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on ICR assessment.
  • Confirmed Objective Response Rate (ORR) based on investigator assessment.
    • Time Frame: An average of approximately 12 months.
    • Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
  • Overall survival (OS).
    • Time Frame: An average of approximately 20 months.
    • OS is the time form the date of first dose of study treatment until death due to any cause.
  • Occurrence of adverse events (AEs) and serious adverse events (SAEs).
    • Time Frame: An average of approximately 14 months.
    • Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
  • Serum concentration of T-DXd.
    • Time Frame: An average of approximately 14 months.
    • Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
  • Serum concentration of total anti-HER2 antibody.
    • Time Frame: An average of approximately 14 months.
    • Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
  • Serum concentration of MAAA-1181a.
    • Time Frame: An average of approximately 14 months.
    • Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for MAAA-1181a.
  • The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.
    • Time Frame: An avarage of approximately 14 months.
    • Individual participant data and descriptive statistics will be provided for data at each time point.

Participating in This Clinical Trial

Inclusion Criteria

  • Adults ≥18 years old. Other age restrictions may apply as per local regulations. – Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS, who have progressed following prior treatment or who have no satisfactory alternative treatment options. – Prior HER2 targeted therapy is permitted. – All patients must provide an FFPE tumor sample for retrospective central HER2 testing. – LVEF ≥50% – ECOG 0-1 Exclusion Criteria:
  • HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. – HER2 mutant NSCLC. – History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening – Lung-specific intercurrent clinically significant severe illnesses. – History of active primary immunodeficiency, known HIV, active HBV or HCV infection – Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals – Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). – Has spinal cord compression or clinically active central nervous system metastases.
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: 120 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • AstraZeneca
    • Collaborator
      • Daiichi Sankyo Co., Ltd.
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Contact(s)
      • AstraZeneca Clinical Study Information Center, 1-877-240-9479, information.center@astrazeneca.com

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