A Study of T-DXd in Patients With Selected HER2-overexpressing Tumors

A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Patients With Selected HER2-overexpressing Tumors (DESTINY PanTumor03)

This is an open-label, multicenter, Phase II study to evaluate the efficacy and safety of trastuzumab deruxtecan for the treatment in locally advanced, unresectable, or metastatic patients with selected HER2 overexpressingsolid tumors which are not eligible for curative therapy.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors (Excluding Gastric Cancer and Breast Cancer)
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Beijing, China, 100142
    • Not yet recruiting
    • Research Site
  • Changchun, China, 130021
    • Not yet recruiting
    • Research Site
  • Changsha, China, 410013
    • Not yet recruiting
    • Research Site
  • Changzhou, China, 213004
    • Not yet recruiting
    • Research Site
  • Chengdu, China, 610041
    • Not yet recruiting
    • Research Site
  • Chongqing, China, 400030
    • Not yet recruiting
    • Research Site
  • Dongyang, China, 322100
    • Not yet recruiting
    • Research Site
  • Guangzhou, China, 510630
    • Not yet recruiting
    • Research Site
  • Guangzhou, China, 510145
    • Not yet recruiting
    • Research Site
  • Haikou, China, 570311
    • Withdrawn
    • Research Site
  • Hangzhou, China, 310022
    • Not yet recruiting
    • Research Site
  • Harbin, China, 150081
    • Recruiting
    • Research Site
  • Hefei, China, 230031
    • Not yet recruiting
    • Research Site
  • Kunming, China, 650118
    • Not yet recruiting
    • Research Site
  • Lishui, China, 323000
    • Not yet recruiting
    • Research Site
  • Nanchang, China, 330029
    • Not yet recruiting
    • Research Site
  • Shanghai, China, 200032
    • Not yet recruiting
    • Research Site
  • Shanghai, China, 200011
    • Not yet recruiting
    • Research Site
  • Shenyang, China, 110016
    • Not yet recruiting
    • Research Site
  • Xuzhou, China, 221009
    • Not yet recruiting
    • Research Site
  • Yinchuan, China, 750004
    • Not yet recruiting
    • Research Site
  • Zhengzhou, China, 450008
    • Not yet recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years of age.
• Locally advanced, unresectable, or metastatic solid tumors based on most recent imaging.
• HER2 overexpression.
• ECOG performance status of 0-1.
• Must provide an existing FFPE tumor sample to centrally determine HER2 expression and other correlatives.
• Has measurable target disease assessed by the investigator based on RECIST 1.1.
• Adequate organ function and bone marrow within 14 days before enrollment.
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent.
• Provision of signed and dated written ICF prior to mandatory study-specific procedures, sampling, or analyses.

Exclusion Criteria:

• Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the gastric body or gastroesophageal junction.
• Has substance abuse or any other medical conditions that may interfere with the patient's participation in the clinical study or evaluation of the clinical study results.
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and concentrated ascites reinfusion therapy.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
• Has unresolved toxicities from previous anti cancer therapy.
• Has any spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
• Uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals, or active infection including tuberculosis.
• Active primary immunodeficiency, known uncontrolled active HIV infection, or active Hepatitis B or C infection.
• Protocol-defined inadequate cardiac function.
• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has a concomitant medical condition that would increase the risk of toxicity in the opinion of the investigator.
• Anti cancer chemotherapy without an adequate treatment washout period prior to randomization.
• Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
• Known hypersensitivity to T-DXd or any excipients of the product or other mAbs.
• Involvement in the planning and/or conduct of the study.
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• Previous enrollment in the present study.
• For females only: Currently pregnant or breast feeding, or who are planning to become pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab deruxtecan	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)	Confirmed ORR by ICR is the proportion of patients who have a confirmed complete response or confirmed partial response, as determined by ICR per RECIST 1.1.	An average of approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR) by investigator assessment	Confirmed ORR by investigator assessment is the proportion of patients who have a confirmed complete response or partial response, as determined by the investigator at local site per RECIST 1.1.	An average of approximately 12 months
Duration of Response (DoR) by Independent Central Review (ICR)	DoR by ICR is defined as the time from the date of first documented response until the date of documented progression (using RECIST 1.1 by ICR) or death in the absence of disease progression.	An average of approximately 12 months
Duration of Response (DoR) by investigator assessment	DoR by investigator assessment is defined as the time from the date of first documented response until the date of documented progression (using RECIST 1.1 by investigator assessment) or death in the absence of disease progression.	An average of approximately 12 months
Disease control rate (DCR) by Independent Central Review (ICR)	The DCR by ICR is defined as the percentage of patients who have a confirmed complete response (CR) or partial response (PR) or stable disease (SD) per RECIST 1.1 by ICR.	An average of approximately 12 months
Disease control rate (DCR) by investigator assessment	The DCR by investigator assessment is defined as the percentage of patients who have a confirmed complete response (CR) or partial response (PR) or stable disease (SD) per RECIST 1.1 by investigator assessment.	An average of approximately 12 months
Confirmed best objective response (BOR) by Independent Central Review (ICR)	BOR by ICR is a patient's best response during their participation in the study up until RECIST 1.1-defined progression by ICR or the last evaluable assessment in the absence of RECIST 1.1-defined progression by ICR.	An average of approximately 12 months
Confirmed best objective response (BOR) by investigator assessment	BOR by investigator assessment is a patient's best response during their participation in the study up until RECIST 1.1 defined progression or the last evaluable assessment in the absence of RECIST 1.1 defined progression.	An average of approximately 12 months
Progression-free survival (PFS) by Independent Central Review (ICR)	PFS by ICR will be defined as the time from the date of enrollment until the date of objective progressive disease (PD) per RECIST 1.1 as assessed by ICR or death.	An average of approximately 12 months
Progression-free survival (PFS) by investigator assessment	PFS by investigator assessment is defined as the time from the date of enrollment until the date of progressive disease (PD) per RECIST 1.1 as assessed by the investigator or death.	An average of approximately 12 months
Overall survival (OS)	OS is defined as the time from the date of enrollment until death due to any cause.	An average of approximately 12 months
Occurrence of adverse events (AEs) and serious adverse events (SAEs)	The grading scales found in the revised NCI CTCAE v5.0 will be utilized for all events.	An average of approximately 12 months
Pharmacokinetics (PK) of T-DXd	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.	An average of approximately 12 months
Immunogenicity of T-DXd	Incidence of anti-drug antibodies against T-DXd in serum at each time point.	An average of approximately 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2024
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): April 17, 2026

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: D781AC00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No