A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors (DPT02)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04482309 |
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Recruitment Status :
Active, not recruiting
First Posted : July 22, 2020
Last Update Posted : February 6, 2024
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: Trastuzumab deruxtecan | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 468 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | 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. |
| Masking: | None (Open Label) |
| Masking Description: | This study is Open-Label Study. |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | August 18, 2020 |
| Actual Primary Completion Date : | June 8, 2023 |
| Estimated Study Completion Date : | July 30, 2027 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1 Cohort 1
Biliary tract cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 2
Bladder cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 3
Cervical cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 4
Endometrial cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 5
Ovarian cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 6
Pancreatic cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 1 Cohort 7
Rare tumors
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 2 Cohort A
Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 2 Cohort B
Any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer)
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 2 Cohort C
HER2 IHC 2+ or 1+ endometrial cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 2 Cohort D
HER2 IHC 2+ or 1+ ovarian cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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Experimental: Part 2 Cohort E
HER2 IHC 2+ or 1+ cervical cancer
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Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Names:
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- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Locally advanced, unresectable, or metastatic disease based on most recent imaging.
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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.
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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.
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04482309
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| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04482309 |
| Other Study ID Numbers: |
D967VC00001 2020-001574-29 ( EudraCT Number ) |
| First Posted: | July 22, 2020 Key Record Dates |
| Last Update Posted: | February 6, 2024 |
| Last Verified: | January 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2 |
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Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases |
Intestinal Diseases Rectal Diseases Trastuzumab Trastuzumab deruxtecan Antineoplastic Agents, Immunological Antineoplastic Agents Immunoconjugates Immunologic Factors Physiological Effects of Drugs |