Trastuzumab deruxtecan: Trastuzumab deruxtecan by intravenous infusion
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
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.
Primary outcome measure(s)
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.
Trial sites (89)
Facility
City
Region
Status
Research Site
Duarte
California
Research Site
Santa Rosa
California
Research Site
Chicago
Illinois
Research Site
Muncie
Indiana
Research Site
Boston
Massachusetts
Research Site
Middletown
New Jersey
Research Site
Harrison
New York
Research Site
New York
New York
Research Site
New York
New York
Research Site
Durham
North Carolina
Research Site
Houston
Texas
Research Site
Seattle
Washington
Research Site
Auchenflower
Australia
Research Site
Blacktown
Australia
Research Site
Camperdown
Australia
Research Site
Heidelberg
Australia
Research Site
Melbourne
Australia
Research Site
Nedlands
Australia
Research Site
Brussels
Belgium
Research Site
Leuven
Belgium
Research Site
Liège
Belgium
Research Site
Porto Alegre
Brazil
Research Site
São Paulo
Brazil
Research Site
Vitória
Brazil
Research Site
Kelowna
British Columbia
Research Site
Ottawa
Ontario
Research Site
Québec
Quebec
Research Site
Montreal
Canada
Research Site
Brno
Czechia
Research Site
Hradec Králové
Czechia
Research Site
Olomouc
Czechia
Research Site
Prague
Czechia
Research Site
Prague
Czechia
Research Site
Delhi
India
Research Site
Gurgaon
India
Research Site
Kolkata
India
Research Site
Mumbai
India
Research Site
Milan
Italy
Research Site
Milan
Italy
Research Site
Naples
Italy
+ 49 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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