Clinical Trials /

A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors

NCT04482309

Description:

This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 tumor-specific cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.

Related Conditions:
  • Biliary Tract Carcinoma
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Endometrial Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors
  • Official Title: A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)

Clinical Trial IDs

  • ORG STUDY ID: D967VC00001
  • NCT ID: NCT04482309

Conditions

  • Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a, T-DXdArm 1

Purpose

This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 tumor-specific cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalCohort 1: Biliary tract cancer
  • Trastuzumab deruxtecan
Arm 2ExperimentalCohort 2: Bladder cancer
  • Trastuzumab deruxtecan
Arm 3ExperimentalCohort 3: Cervical cancer
  • Trastuzumab deruxtecan
Arm 4ExperimentalCohort 4: Endometrial cancer
  • Trastuzumab deruxtecan
Arm 5ExperimentalCohort 5: Ovarian cancer
  • Trastuzumab deruxtecan
Arm 6ExperimentalCohort 6: Pancreatic cancer
  • Trastuzumab deruxtecan
Arm 7ExperimentalCohort 7: Rare tumors
  • Trastuzumab deruxtecan

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced, unresectable, or metastatic disease based on most recent imaging.

          -  The respective cohorts for patient inclusion are:

               -  Cohort 1: Biliary tract cancer

               -  Cohort 2: Bladder cancer

               -  Cohort 3: Cervical cancer

               -  Cohort 4: Endometrial cancer

               -  Cohort 5: Epithelial ovarian cancer

               -  Cohort 6: Pancreatic cancer

               -  Cohort 7: Rare tumors: This cohort will consist of patients with tumors that
                  express HER2, excluding the tumors mentioned above, and breast, non-small cell
                  lung cancer, gastric cancer, and colorectal cancer.

          -  Progressed following prior treatment or who have no satisfactory alternative treatment
             option.

          -  Prior HER2 targeting therapy is permitted.

          -  HER2 expression for eligibility may be based on local or central assessment.

          -  Has measurable target disease assessed by the Investigator based on RECIST version
             1.1.

          -  Has protocol- defined adequate organ function including cardiac, renal and hepatic
             function.

        Exclusion Criteria:

          -  History of non-infectious pneumonitis/ILD that required steroids, current ILD, or
             where suspected ILD that cannot be ruled out by imaging at screening

          -  Lung-specific intercurrent clinically significant severe illnesses

          -  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

          -  Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.

          -  Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or
             rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small
             cell lung cancer.

          -  Medical conditions that may interfere with the subject's participation in the study.
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
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.

Secondary Outcome Measures

Measure:Duration of response (DoR)
Time Frame:An average of approximately 18 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.
Measure:Disease control rate (DCR)
Time Frame:An average of approximately 18 months
Safety Issue:
Description:DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
Measure:Progression free survival (PFS)
Time Frame:An average of approximately 18 months
Safety Issue:
Description:PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.
Measure:Proportion of patients alive and progression-free at 6 months and 12 months
Time Frame:Up to 12 months
Safety Issue:
Description:The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
Measure:Overall survival (OS)
Time Frame:An average of approximately 30 months
Safety Issue:
Description:OS is the time from date of first dose of study treatment until death due to any cause.
Measure:Proportion of patients alive at 6 and 12 months
Time Frame:Up to 12 months
Safety Issue:
Description:The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Measure:Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:An average of approximately 24 months
Safety Issue:
Description:Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Measure:Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181
Time Frame:An average of approximately 24 months
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
Measure:The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd
Time Frame:An average of approximately 24 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:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2

Last Updated

June 9, 2021