DS-8201a in HER2-positive Gastric Cancer that cannot be surgically removed or has spread

Phase 1

• Conditions: 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: 100000004864; MedDRA version: 21.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001512-34-ES
• Lead Sponsor: Daiichi Sankyo Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-26
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 72

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 based on a new tissue sample obtained after progression on or after a trastuzumabcontaining regimen. If a tissue sample was already collected after discontinuation of first-line treatment with a trastuzumab-containing regimen, it is acceptable to consider this a new biopsy for the purpose of this study.

- 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 independent central review.

- Has left ventricular ejection fraction (LVEF) =50% within 28 days before enrollment per echocardiogram
(ECHO)/multigated acquisition (MUGA) scan.

- 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 4.5 months after the last dose of study drug.

- Adequate renal function, defined as creatinine clearance =30 mL/min, as calculated using the Cockcroft-Gault equation.

- Adequate hepatic function, defined as total bilirubin =1.5 × upper limit of normal (ULN); serum albumin =2.8 g/dL; aspartate transaminase (AST)/alanine transaminase (ALT) =3 × ULN in the absence of liver metastases or =5 × ULN in the presence of liver metastases.
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

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 before enrollment
- 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 enrollment
- History of unstable angina or serious cardiac arrhythmia requiring treatment
- 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) or pneumonitis that required corticosteroid therapy or has current ILD/pneumonitis or is suspected to have such diseases by imaging during Screening.

- Clinically significant corneal disease, in the opinion of the Investigator.

- Pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). (Drainage 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 enrollment (1 week for stereotactic radiotherapy).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified