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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
477
Trastuzumab deruxtecan by intravenous infusion
Research Site
Duarte, California, United States
Research Site
Santa Rosa, California, United States
Research Site
Chicago, Illinois, United States
Research Site
Muncie, Indiana, United States
Research Site
Boston, Massachusetts, United States
Research Site
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.
Time frame: An average of approximately 6 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.
Time frame: 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).
Time frame: 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.
Time frame: An average of approximately 6 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).
Time frame: 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.
Time frame: An average of approximately 14 months
Proportion of patients alive at 6 and 12 months
The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: An average of approximately 6 months
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Middletown, New Jersey, United States
Research Site
Harrison, New York, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
Durham, North Carolina, United States
...and 79 more locations