Unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma that has progressed on or after a trastuzumab-containing regimen MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 10029104 - N
Conditions
Interventions
Product Name: DS-8201a
Product Code: DS-8201a
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Trastuzumab deruxtecan
Current Sponsor code: DS-8201A
Other descriptive
Sponsors
Daiichi Sankyo Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: - Men or women =18 years old (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years old.) - Has pathologically documented gastric or GEJ cancer that is: - Unresectable or metastatic - Centrally confirmed HER2-positive disease (immunohistochemistry [IHC]3+, IHC2+/in-situ hybridization [ISH]+) as determined according to American Society of Clinical Oncology – College of American Pathologists (ASCO CAP) guidelines new tumor biopsy obtained after progression on or after a first-line trastuzumab-containing regimen. If a tumor biopsy was already collected after discontinuation of first-line treatment with a trastuzumab-containing regimen, it is acceptable to consider the biopsy to be a new biopsy for the purpose of this study, provided that there is sufficient tissue for exploratory biomarker studies. - Has experienced disease progression during or after first-line therapy with a trastuzumab-containing regimen (brand or approved biosimilar). Note: Prior adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing adjuvant therapy. - Has at least 1 measurable lesion per RECIST v1.1 as confirmed by the investigator review. - Has left ventricular ejection fraction (LVEF) =50% within 28 days before first dose per echocardiogram (ECHO)/multigated acquisition (MUGA) scan. - Has adequate organ function within 14 days before first dose, defined as in the protocol - Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: - Use of anticancer therapy after first-line treatment with a trastuzumab-containing regimen. - Uncontrolled or significant cardiovascular disease, including any of the following: - History of myocardial infarction (MI) within 6 months of first dose - History of symptomatic congestive heart failure (New York Heart Association Class II to IV) - Troponin levels consistent with MI as defined according to the manufacturer within 28 days prior to first dose - Corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male) based on Screening triplicate 12-lead electrocardiogram (ECG) - History of (non-infectious) interstitial lung disease (ILD)/ pneumonitis that required corticosteroid therapy or has current ILD/pneumonitis or is suspected to have such diseases by imaging during Screening. - Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the first dose, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy. - Pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). (Drainage and Cell-free and CART are not allowed within 2 weeks prior to or during Screening.) - Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Subjects with clinically inactive brain metastases may be included in the study. - Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study recruitment (1 week for stereotactic radiotherapy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of trastuzumab deruxtecan based on the confirmed objective response rate (ORR) by independent central review by using Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1;Secondary Objective: - To evaluate the efficacy of Trastuzumab Deruxtecan on progression-free survival (PFS), based on independent central review using RECIST v1.1. Other secondary objectives: - To further evaluate the efficacy of Trastuzumab Deruxtecan by using the endpoint of OS - To further evaluate the efficacy of Trastuzumab Deruxtecan by using RECIST v1.1 for endpoints of PFS and ORR based on Investigator assessment, and duration of response (DoR) based on independent central review and Investigator assessment - To determine the pharmacokinetics (PK) of Trastuzumab Deruxtecan in serum - To further evaluate the safety of Trastuzumab Deruxtecan based on treatment-emergent adverse events (TEAEs) and anti-drug antibodies (ADAs) - To evaluate Health Economics and Outcomes Research (HEOR) endpoints based on patient-reported outcomes (PROs);Primary end point(s): Confirmed ORR (objective response rate) based on independent central review;Timepoint(s) of evaluation of this end point: Analysis of ORR will be performed for all enrolled subjects at the 18-week tumor assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-Free Survival (PFS) , based on independent central review using RECIST v1.1. Other Secondary Endpoints: - PFS, based on Investigator assessment - Objective response rate (ORR), based on Investigator assessment - Overall survival (OS) - Duration of Response (DoR), based on independent central review and Investigator assessment ;Timepoint(s) of evaluation of this end point: Along the study. Based on independent central review | — |
Countries
Belgium, Italy, Spain, United Kingdom, United States
Outcome results
None listed