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

Study Overview
=================
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 enroll 7 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.

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)

Conditions
-----------------
Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors

Intervention / Treatment
-----------------
* Drug: Trastuzumab deruxtecan


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will consist of seven cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, Pancreatic cancer, and rare tumors.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Cohort 1: Biliary tract cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 2<br>Cohort 2: Bladder cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 3<br>Cohort 3: Cervical cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 4<br>Cohort 4: Endometrial cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 5<br>Cohort 5: Ovarian cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 6<br>Cohort 6: Pancreatic cancer | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: T-DXd;|
| Experimental: Arm 7<br>Cohort 7: Rare tumors | Drug: Trastuzumab deruxtecan<br>* Trastuzumab deruxtecan by intravenous infusion<br>* Other names: 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 41 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 41 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 41 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 41 months | 
| 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 | 
| 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 41 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 | 
| 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 41 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 41 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 41 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2