TDXd + Chemotherapy + Pembrolizumab for Gastric Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores a new combination of treatments for individuals with advanced gastric or gastroesophageal junction cancer that is HER2-positive, indicating the presence of a specific protein that promotes growth. The trial tests the effectiveness and safety of adding trastuzumab deruxtecan, a new drug, to standard chemotherapy and pembrolizumab, an immunotherapy drug. The trial includes different groups: one for those with higher levels of a protein called PD-L1 in their tumors and another for those with lower levels. Suitable candidates for this trial have advanced HER2-positive gastric cancer that hasn't been treated before and have measurable tumors. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that trastuzumab deruxtecan (T-DXd) with chemotherapy is generally well-tolerated. In studies, most patients experienced manageable side effects. However, serious lung issues, such as interstitial lung disease (ILD), occurred in about 0.9% of patients, meaning fewer than 1 in 100 patients had severe lung problems.
Trastuzumab, often combined with chemotherapy and pembrolizumab, has also demonstrated good safety results. It is usually well-tolerated, with few serious side effects. Some individuals might experience immune-related reactions when trastuzumab is combined with a PD-1 inhibitor like pembrolizumab. These reactions occurred in about 12.5% of cases, or roughly 1 in 8 patients.
Overall, these treatments have been approved for other conditions, indicating a favorable safety profile. Participants in this trial can expect similar safety outcomes based on past data.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments for gastric cancer because they combine innovative targeted therapies with traditional chemotherapy and immunotherapy. Trastuzumab Deruxtecan (T-DXd) and Trastuzumab are antibody-drug conjugates that deliver chemotherapy directly to cancer cells, potentially increasing effectiveness while minimizing harm to healthy cells. Pembrolizumab, an immunotherapy drug, works by unleashing the immune system to attack cancer cells more vigorously. By integrating these advanced therapies with standard chemotherapy, these treatment combinations aim to enhance cancer-fighting power and improve patient outcomes compared to traditional treatments alone.
What evidence suggests that this trial's treatments could be effective for gastric cancer?
This trial will evaluate different treatment combinations for HER2-positive stomach or gastroesophageal junction cancer. Participants in Arm M1 will receive trastuzumab deruxtecan (T-DXd) combined with fluoropyrimidine (5-FU or capecitabine) and pembrolizumab. Research shows that this combination effectively targets advanced HER2-positive stomach and esophageal cancers.
In Arm M2, participants will receive trastuzumab combined with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab. Studies indicate that adding pembrolizumab to trastuzumab and chemotherapy significantly improves survival in patients with HER2-positive stomach cancer, extending life by several months compared to standard treatments.
The exploratory cohorts will further assess these combinations without pembrolizumab. Arm E1 will receive T-DXd with fluoropyrimidine, while Arm E2 will receive trastuzumab with platinum-based chemotherapy. Evidence suggests these treatment combinations could be effective for HER2-positive stomach or gastroesophageal junction cancer.46789Are You a Good Fit for This Trial?
This trial is for adults with advanced HER2-positive gastric or gastroesophageal junction cancer that hasn't been treated before. They must have a specific protein (PD-L1 CPS ≥1) in the main group, or PD-L1 CPS <1 in another group being studied. Participants need to provide tumor samples and can join even if they had certain treatments over 6 months ago.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive T-DXd plus fluoropyrimidine plus pembrolizumab or standard of care chemotherapy plus trastuzumab plus pembrolizumab
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Chemotherapy
- Pembrolizumab
- Trastuzumab
- Trastuzumab Deruxtecan
Find a Clinic Near You
Who Is Running the Clinical Trial?
Daiichi Sankyo
Lead Sponsor
Hiroyuki Okuzawa
Daiichi Sankyo
Chief Executive Officer
Degree in Social Sciences from Hitotsubashi University
Yuki Abe
Daiichi Sankyo
Chief Medical Officer since 2023
MD
Merck Sharp & Dohme LLC
Industry Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University