E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma that has progressed on or after a trastuzumab-containing regimen
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E.1.1.1 | Medical condition in easily understood language |
HER2-POSITIVE, UNRESECTABLE OR METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION (GEJ) ADENOCARCINOMA
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071114 |
E.1.2 | Term | Metastatic gastric adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066354 |
E.1.2 | Term | Adenocarcinoma of the gastroesophageal junction |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
- 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) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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).
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E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed ORR (objective response rate) based on independent central review |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of ORR will be performed for all enrolled subjects at the 18-week tumor assessment.
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Along the study. Based on independent central review
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
Belgium |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study will occur when all enrolled subjects have either completed their last scheduled visit or died or withdrawn from study participation, which is anticipated to occur approximately 12 months after the last subject is enrolled |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |