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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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 / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Estimated): 468
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Auchenflower, Australia, 4066
    • Research Site
  • Camperdown, Australia, 2050
    • Research Site
  • Heidelberg, Australia, 3084
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
• Belgium
  • Brussels, Belgium, 1090
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Canada
  • Montreal, Canada, H3T 1E2
    • Research Site
  • Quebec, Canada, G1J 1Z4
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 77900
    • Research Site
  • Praha 5, Czechia, 150 06
    • Research Site
  • Praha 8, Czechia, 180 81
    • Research Site
• India
  • Delhi, India, 110085
    • Research Site
  • Gurgaon, India, 122001
    • Research Site
  • Kolkata, India, 700160
    • Research Site
  • Mumbai, India, 400012
    • Research Site
• Italy
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20162
    • Research Site
  • Rome, Italy, 168
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 5505
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Research Site
  • Delft, Netherlands, 2625 AD
    • Research Site
  • Groningen, Netherlands, 9700
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Kraków, Poland, 31-501
    • Research Site
  • Poznan, Poland, 60-780
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Russian Federation
  • Kaluga, Russian Federation, 248007
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 115419
    • Research Site
  • Moscow, Russian Federation, 117997
    • Research Site
  • Moscow, Russian Federation, 121205
    • Research Site
  • Moscow, Russian Federation, 143423
    • Research Site
  • Moscow, Russian Federation, 143442
    • Research Site
  • Saint Petersburg, Russian Federation, 195271
    • Research Site
  • Saint-Petersburg, Russian Federation, 197758
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40705
    • Research Site
  • Tainan, Taiwan, 736
    • Research Site
  • Taipei, Taiwan, 100
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Tao-Yuan, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10210
    • Research Site
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Ongkharak, Thailand, 26120
    • Research Site
• United Kingdom
  • London, United Kingdom, SW2 6JJ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Research Site
  • New York
    • Harrison, New York, United States, 10604
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Cohort 1; Biliary tract cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 2; Bladder cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 3; Cervical cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 4; Endometrial cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 5; Ovarian cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 6; Pancreatic cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 1 Cohort 7; Rare tumors	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 2 Cohort A; Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 2 Cohort B; Any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer)	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 2 Cohort C; HER2 IHC 2+ or 1+ endometrial cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 2 Cohort D; HER2 IHC 2+ or 1+ ovarian cancer	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Experimental: Part 2 Cohort E; HER2 IHC 2+ or 1+ cervical cancer	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
Objective Response Rate (ORR)	Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.	An average of approximately 6 months

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): June 8, 2023
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: D967VC00001; 2020-001574-29 (EudraCT Number)

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.

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.

• IPD Sharing 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.

IPD Sharing 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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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