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
Conditions
Keywords
T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2
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.
Interventions
DRUGTrastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Sponsors
AstraZeneca
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is Open-Label Study.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | 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) | 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) | 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 | Up to 12 months | The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates). |
| Overall survival (OS) | 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 | 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) | 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 | 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 | An average of approximately 6 months | Individual participant data and descriptive statistics will be provided for data at each time point. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, India, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Outcome results
None listed