A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors (DPT02)

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ClinicalTrials.gov Identifier: NCT04482309

Recruitment Status : Active, not recruiting

First Posted : July 22, 2020

Last Update Posted : February 6, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

Daiichi Sankyo Co., Ltd.

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

July 20, 2020

First Posted Date ^ICMJE

July 22, 2020

Last Update Posted Date

February 6, 2024

Actual Study Start Date ^ICMJE

August 18, 2020

Actual Primary Completion Date

June 8, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Objective Response Rate (ORR) [ Time Frame: An average of approximately 6 months ]

Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Original Primary Outcome Measures ^ICMJE

Objective Response Rate (ORR) [ 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.

Change History

Current Secondary Outcome Measures ^ICMJE

Duration of response (DoR) [ Time Frame: An average of approximately 6 months ]
DOR is defined as the time from the date of first documented response until the date of documented progression or death.
Disease control rate (DCR) [ Time Frame: An average of approximately 6 months ]
DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
Progression free survival (PFS) [ Time Frame: An average of approximately 6 months ]
PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.
Proportion of patients alive and progression-free at 6 months and 12 months [ Time Frame: Up to 12 months ]
The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
Overall survival (OS) [ Time Frame: An average of approximately 14 months ]
OS is the time from date of first dose of study treatment until death due to any cause.
Proportion of patients alive at 6 and 12 months [ Time Frame: Up to 12 months ]
The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: An average of approximately 8 months ]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181 [ Time Frame: An average of approximately 8 months ]
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
The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd [ Time Frame: An average of approximately 6 months ]
Individual participant data and descriptive statistics will be provided for data at each time point.

Original Secondary Outcome Measures ^ICMJE

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

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

Brief Summary

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 consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.

Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Masking: None (Open Label)
Masking Description:

This study is Open-Label Study.

Primary Purpose: Treatment

Condition ^ICMJE

Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer
Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer

Intervention ^ICMJE

Drug: Trastuzumab deruxtecan

Trastuzumab deruxtecan by intravenous infusion

Other Names:

DS-8201a
T-DXd

Study Arms ^ICMJE

Experimental: Part 1 Cohort 1
Biliary tract cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 2
Bladder cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 3
Cervical cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 4
Endometrial cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 5
Ovarian cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 6
Pancreatic cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 1 Cohort 7
Rare tumors

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 2 Cohort A
Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 2 Cohort B
Any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer)

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 2 Cohort C
HER2 IHC 2+ or 1+ endometrial cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 2 Cohort D
HER2 IHC 2+ or 1+ ovarian cancer

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Part 2 Cohort E
HER2 IHC 2+ or 1+ cervical cancer

Intervention: Drug: Trastuzumab deruxtecan

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

468

Original Estimated Enrollment ^ICMJE

280

Estimated Study Completion Date ^ICMJE

July 30, 2027

Actual Primary Completion Date

June 8, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Locally advanced, unresectable, or metastatic disease based on most recent imaging.
Part 1: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.
Part 2:The respective cohorts for patient inclusion are:
- Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
- Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
- Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.
- Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.
- Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.
Progressed following prior treatment or who have no satisfactory alternative treatment option.
Prior HER2 targeting therapy is permitted.
HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric cancer.
- Part 1: IHC 3+ or IHC 2+ by local or central assessment
- Part 2: IHC and ISH results by central assessment as pre-defined for each cohort
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 for Part 1. For Part 2, patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.
Medical conditions that may interfere with the subject's participation in the study.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 120 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Australia, Belgium, Canada, Czechia, India, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, Thailand, United Kingdom, United States

Removed Location Countries

Brazil

Administrative Information

NCT Number ^ICMJE

NCT04482309

Other Study ID Numbers ^ICMJE

D967VC00001
2020-001574-29 ( EudraCT Number )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
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. All request 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 shared.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:	When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home