Combination Therapies for Esophageal Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores new treatment combinations for esophageal squamous cell carcinoma (ESCC), a cancer that begins in the esophagus lining. Researchers are assessing the safety and effectiveness of these treatments, particularly when combining pembrolizumab (an immunotherapy that aids the immune system in fighting cancer) with chemotherapy or investigational drugs like ifinatamab deruxtecan (I-DXd, which directly targets cancer cells). The goal is to determine if these combinations can shrink or eliminate the cancer. Suitable participants have ESCC that cannot be surgically removed or has spread, and they have not yet undergone systemic anticancer therapy for this condition. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that pembrolizumab, used to treat esophageal cancer, effectively targets tumors and is generally well-tolerated by patients. Some participants in studies have experienced common side effects like tiredness and skin reactions, but these are usually manageable.
For the investigational treatment ifinatamab deruxtecan (I-DXd), studies are ongoing, focusing on its safety. While specific results remain limited, its presence in clinical trials indicates it has passed initial safety checks.
Sacituzumab tirumotecan, another investigational drug, has been studied for safety and tolerability when combined with other treatments. Early results are promising, with efforts underway to find the best dose to minimize side effects.
Overall, these treatments are still under investigation, and researchers are actively studying their safety and effectiveness. Participants in these trials receive close monitoring to manage any side effects.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments for esophageal cancer because they combine innovative therapies with existing ones to potentially enhance effectiveness. Pembrolizumab, an immunotherapy drug, is used in combination with different agents like I-DXd and sacituzumab tirumotecan, both of which are antibody-drug conjugates (ADCs). ADCs are unique because they deliver chemotherapy directly to cancer cells, sparing healthy cells and potentially reducing side effects. Additionally, incorporating pembrolizumab with these ADCs may enhance the immune system's ability to fight cancer. This approach offers a fresh angle compared to traditional chemotherapy and radiation, aiming to improve outcomes for patients with esophageal cancer.
What evidence suggests that this trial's treatments could be effective for esophageal cancer?
Research has shown that combining pembrolizumab with chemotherapy can improve survival rates for patients with esophageal cancer. In this trial, one arm will test pembrolizumab with chemotherapy. Studies have found that this combination helps patients live longer without their cancer worsening, with an average of 6.3 months compared to 5.8 months for chemotherapy alone. Another study found that the 5-year survival rate was higher for those taking pembrolizumab compared to those taking a placebo.
Another arm of this trial will evaluate the combination of pembrolizumab with sacituzumab tirumotecan, which has also shown encouraging results. In patients with advanced cancer, nearly half (47%) responded well to this treatment. These findings suggest that these new therapies might offer hope for treating esophageal cancer.678910Who Is on the Research Team?
Medical Director
Principal Investigator
Merck Sharp & Dohme LLC
Are You a Good Fit for This Trial?
This trial is for adults with advanced esophageal squamous cell carcinoma that can't be removed by surgery or has spread. They must have measurable cancer, manageable side effects from past treatments, and controlled hepatitis B or C if present. HIV-positive individuals on effective therapy can join. Good physical health (ECOG 0-1) is required.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive pembrolizumab with or without chemotherapy, including investigational agents, for up to approximately 2 years
Safety Lead-In
Participants are monitored for dose limiting toxicities during the initial phase of treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- I-DXd
- Pembrolizumab
Trial Overview
The study tests pembrolizumab (immunotherapy) combined with investigational drugs like I-DXd (a targeted therapy), possibly alongside standard chemotherapy agents such as 5-FU and oxaliplatin, to see how well patients tolerate them and their effect on esophageal cancer.
How Is the Trial Designed?
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Treatment groups
Experimental Treatment
Active Control
Participants will receive 400 mg pembrolizumab via IV infusion Q6W on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years). Participants will also receive sacituzumab tirumotecan 4 mg/kg via IV infusion Days 1, 15, and 29 every 42 day cycle until PD or toxicity, 5-FU 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-DXd via IV infusion q3w until PD or toxicity, 5-FU 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, 60mg/m\^2 oxaliplatin via IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
Participants will receive 200 mg pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive I-DXd up to 12 mg/kg via IV infusion Q3W until PD or toxicity, 5-FU 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle for up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-XDd Q3W via IV infusion until PD or toxicity.
Participants will receive 400 mg of pembrolizumab via intravenous (IV) infusion every six weeks (Q6W) on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years), and mFOLFOX6 chemotherapy: oxaliplatin 85 mg/m\^2 via IV infusion every 2 weeks (Q2W) until progressive disease (PD) or toxicity; leucovorin 400 mg/m2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity; 5-fluorouracil (5-FU) 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLC
Lead 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
Daiichi Sankyo
Industry 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
Citations
First-line pembrolizumab plus chemotherapy versus ...
In pts with adenocarcinoma OS HR was 0.73 (95% CI, 0.55-0.99). The 24-mo OS rate in all pts was 26.3% vs 16.1%. Median PFS was longer with ...
Long-term efficacy and predictors of pembrolizumab-based ...
The 12-mo OS rate among all patients was 78.8% and the 18-mo OS rate was 72.7%. 9 patients died due to tumor progression and 7 patients died due ...
Long-Term Follow-up Affirms Benefit of Pembrolizumab ...
Median progression-free survival was 6.3 months with pembrolizumab plus chemotherapy vs 5.8 months with chemotherapyalone (HR = 0.64). Hazard ...
4.
onclive.com
onclive.com/view/dr-shah-on-5-year-outcomes-with-pembrolizumab-chemo-in-esophageal-cancerDr Shah on 5-Year Outcomes With Pembrolizumab/Chemo ...
The 5-year OS rates were 10.6% and 3.0% in the pembrolizumab and placebo arms, respectively. The median progression-free survival (PFS) was 6.3 ...
First-line pembrolizumab plus chemotherapy for advanced ...
First-line pembrolizumab plus chemotherapy (pembrolizumab–chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus ...
KEYMAKER-U06 substudy 06E: A phase 1/2 open-label, ...
KEYMAKER-U06 is an open-label, phase 1/2, umbrella platform study designed to evaluate investigational agents with or without pembrolizumab and/or chemotherapy ...
NCT06780111 | Substudy 06E: Umbrella Study of ...
The main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them.
8.
humanforschung-schweiz.ch
humanforschung-schweiz.ch/en/trial-search/study-detail/66665/translate/en/?cHash=14921c5135d83841f46842cc1dec7911Clinical Study of Ifinatamab Deruxtecan (I-DXd, MK-2400 ...
This study aims to determine whether the tested drug combinations are safe and effective for the treatment of esophageal squamous cell carcinoma.
Efficacy and safety of combined treatment with ...
Pembrolizumab has demonstrated antitumor activity in patients with advanced esophageal cancer in previous studies. Few studies have assessed ...
Efficacy and safety of pembrolizumab (pembro) alone or in ...
Efficacy and safety of pembrolizumab (pembro) alone or in combination with ... Here we report long-term efficacy and safety data of all cohorts.
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