Clinical Trials /

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

NCT04639219

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: D967MC00001
  • NCT ID: NCT04639219

Conditions

  • Advanced Solid Tumors With HER2 Mutation

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a (T-DXd)T-DXd

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
T-DXdExperimentalT-DXd monotherapy
  • Trastuzumab deruxtecan

Eligibility Criteria

        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.
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate by RECIST 1.1 based on independent central review (ICR).
Time Frame:An average of approximately 12 months.
Safety Issue:
Description: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 Outcome Measures

Measure:Duration of response (DoR) based on ICR assessment.
Time Frame:An average of approximately 12 months.
Safety Issue:
Description: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.
Measure:Disease control rate (DCR) based on ICR assessment.
Time Frame:An average of approximately 12 months.
Safety Issue:
Description: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.
Measure:Progression free survival (PFS) based on ICR assessment.
Time Frame:An average of approximately 12 months.
Safety Issue:
Description:PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on ICR assessment.
Measure:Confirmed Objective Response Rate (ORR) based on investigator assessment.
Time Frame:An average of approximately 12 months.
Safety Issue:
Description: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
Measure:Overall survival (OS).
Time Frame:An average of approximately 20 months.
Safety Issue:
Description:OS is the time form the date of first dose of study treatment until death due to any cause.
Measure:Occurrence of adverse events (AEs) and serious adverse events (SAEs).
Time Frame:An average of approximately 14 months.
Safety Issue:
Description:Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Measure:Serum concentration of T-DXd.
Time Frame:An average of approximately 14 months.
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
Measure:Serum concentration of total anti-HER2 antibody.
Time Frame:An average of approximately 14 months.
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
Measure:Serum concentration of MAAA-1181a.
Time Frame:An average of approximately 14 months.
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for MAAA-1181a.
Measure:The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.
Time Frame:An avarage of approximately 14 months.
Safety Issue:
Description:Individual participant data and descriptive statistics will be provided for data at each time point.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • HER2
  • T-DXd
  • DS-8201a
  • Trastuzumab Deruxtecan
  • Metastatic
  • Solid Tumors
  • Histology Agnostic

Last Updated

November 20, 2020