Trastuzumab Deruxtecan for Subjects with HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma after Progression on or After a Trastuzumab-Containing Regimen

JRCT ID: jRCT2031200369

Registered date:19/02/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Gastric Cancer, Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
• Date of first enrollment: 21/05/2021
• Target sample size: 490
• Countries of recruitment: Argentina,Japan,Belgium,Japan,Brazil,Japan,Chile,Japan,China,Japan,France,Japan,Germany,Japan,Hong Kong,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Russia,Japan,Singapore,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Trastuzumab deruxtecan
Participants who will be randomized to receive a 6.4 mg/kg intravenous (IV) dose of trastuzumab deruxtecan once every 3 weeks on Day 1 of each 21-day cycle.

- Active Comparator: Ramucirumab + paclitaxel
Participants who will be randomized to receive a 8 mg/kg IV dose of ramucirumab on Days 1 and 15 in combination with 80 mg/m^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.

Outcome(s)

• Primary Outcome: Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel

Secondary Outcome

- Progression-free Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
- Objective Response Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
- Duration of Response in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
- Disease Control Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
- Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and Physical Examination Findings
- Serum Concentrations for Trastuzumab Deruxtecan, total anti-HER2 antibody, and Active Metabolite MAAA-
- Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
The immunogenicity of trastuzumab deruxtecan will be assessed.
- Percentage of Participants Who Have Treatment-emergent ADAs
The immunogenicity of trastuzumab deruxtecan will be assessed.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Adults (according to local regulation) and able to provide informed consent for study participation.
- Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease).
- Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. 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.
- Locally or centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.
- Eastern Cooperative Oncology Group performance status of 0 or 1 at both Screening and within 3 days prior to randomization.
- Adequate bone marrow, renal, and hepatic function within 14 days of randomization.

Exclude criteria

- Use of anticancer therapy after trastuzumab-containing treatment
- Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV).
- Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to >470 msec (female subjects) or >450 msec (male subjects) based on average of the Screening triplicate12-lead ECG.
- Has a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). Drainage and CART must be at least 2 weeks prior to Screening.
- Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening.
- Prior pneumonectomy.
- 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.
- Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
- History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd.
- History of severe hypersensitivity reactions to other monoclonal antibodies or any components used in the ramucirumab drug product preparation
- Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy such as peripheral neuropathy, Grade 2.
- Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever >38.0 C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome
- Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade >1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator
- Has history of receiving live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04704934