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.
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
| Drug | Synonyms | Arms |
|---|
| Trastuzumab deruxtecan | DS-8201a, T-DXd | Arm 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
| Name | Type | Description | Interventions |
|---|
| Arm 1 | Experimental | Cohort 1: Biliary tract cancer | |
| Arm 2 | Experimental | Cohort 2: Bladder cancer | |
| Arm 3 | Experimental | Cohort 3: Cervical cancer | |
| Arm 4 | Experimental | Cohort 4: Endometrial cancer | |
| Arm 5 | Experimental | Cohort 5: Ovarian cancer | |
| Arm 6 | Experimental | Cohort 6: Pancreatic cancer | |
| Arm 7 | Experimental | Cohort 7: Rare tumors | |
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
August 12, 2021
