A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06E

New esophageal cancer treatments tested in combination therapy study

NCT: NCT06780111 · Status: RECRUITING · Phase: Phase 2 · Sponsor: Merck Sharp & Dohme LLC · Started: 2025-07-30 · Est. Completion: 2032-01-04

Plain English Summary

Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06) is a Phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC studying Esophageal Squamous Cell Carcinoma. This study tests new investigational drugs combined with pembrolizumab (an immunotherapy) and sometimes chemotherapy for advanced or metastatic esophageal cancer. It is for patients with a specific type of esophageal cancer (squamous cell carcinoma) that has spread and cannot be fully removed by surgery, and who have not received prior treatment for this advanced stage. Participation involves receiving study treatments and regular medical check-ups to monitor for side effects and cancer response. Alternatives may include standard chemotherapy or immunotherapy regimens. The study aims to find safer and more effective treatment combinations for this difficult-to-treat cancer. The trial aims to enroll 298 participants.

Official Summary

Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts. Available treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. Researchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. 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. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have been diagnosed with squamous cell carcinoma of the esophagus that has spread and cannot be removed by surgery, and this is your first treatment for this advanced stage. You cannot join if you have already received treatment for advanced or metastatic esophageal cancer, have certain medical conditions like uncontrolled effusions or significant heart problems, or have had prior treatment with similar immunotherapy drugs. Participants must be generally healthy with good organ function and an ECOG performance status of 0 or 1 (meaning you are able to carry out all self-care but cannot do strenuous activities). Specific health conditions like active autoimmune disease, recent infections, or severe lung issues may prevent participation. This trial is studying Esophageal Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the new drug combinations are by looking at dose-limiting toxicities and overall side effects, and how well the cancer responds by measuring tumor shrinkage. The specific primary outcome measures are: Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase (Up to approximately 28 days); Percentage of Participants who Experience an Adverse Event (AE) (Up to approximately 77 months); Objective Response Rate (ORR) (Up to approximately 77 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for more effective first-line treatments for advanced esophageal squamous cell carcinoma, a cancer with limited options and poor outcomes. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Esophageal Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial, sponsored by Merck, explores novel combinations for a specific cancer type, indicating a focus on expanding the utility of pembrolizumab and potentially introducing new targeted therapies Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific investigational drugs being tested, potential side effects, and how this trial treatment compares to standard options. Be prepared for regular clinic visits for infusions, blood tests, scans to check your cancer, and to report any new symptoms or side effects promptly. Understand that you may be randomly assigned to receive different combinations of the study drugs. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

Inclusion Criteria

The main inclusion criteria include but are not limited to the following:

* Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting.
* Has measurable disease per RECIST 1.1 as assessed by the local site. investigator or designee/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
* Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Has adequate organ function.

Exclusion Criteria

The main exclusion criteria include but are not limited to the following:

* Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.
* Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula.
* Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.
* Has clinically significant corneal disease, history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
* Has inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value \>470 msec.
* Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
* Has peripheral neuropathy ≥ Grade 2.
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has had (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and/or suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at Screening.
* Has active infection requiring systemic therapy.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.

Trial Locations

Frequently Asked Questions

What is clinical trial NCT06780111?

NCT06780111 is a Phase 2 INTERVENTIONAL study titled "Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)." It is currently recruiting and is sponsored by Merck Sharp & Dohme LLC. The trial targets enrollment of 298 participants.

What conditions does NCT06780111 study?

This trial investigates treatments for Esophageal Squamous Cell Carcinoma. The primary condition under study is Esophageal Squamous Cell Carcinoma.

What treatments are being tested in NCT06780111?

The interventions being studied include: Pembrolizumab (BIOLOGICAL), I-DXd (BIOLOGICAL), Leucovorin (DRUG), Levoleucovorin (DRUG), 5-Fluorouracil (5-FU) (DRUG). IV infusion

What does Phase 2 mean for NCT06780111?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT06780111?

This trial is currently "Recruiting." It started on 2025-07-30. The estimated completion date is 2032-01-04.

Who is sponsoring NCT06780111?

NCT06780111 is sponsored by Merck Sharp & Dohme LLC. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06780111?

The trial aims to enroll 298 participants. The trial is currently recruiting and accepting new participants.

How is NCT06780111 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.

What are the primary outcomes being measured in NCT06780111?

The primary outcome measures are: Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase (Up to approximately 28 days); Percentage of Participants who Experience an Adverse Event (AE) (Up to approximately 77 months); Objective Response Rate (ORR) (Up to approximately 77 months). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06780111 being conducted?

This trial is being conducted at 20 sites, including Pittsburgh, Pennsylvania; Natal, Rio Grande do Norte; Porto Alegre, Rio Grande do Sul; Port Montt, Los Lagos Region and 16 more sites (United States, Brazil, Chile).

Where can I find official information about NCT06780111?

The official record for NCT06780111 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06780111. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06780111 testing in simple terms?

This study tests new investigational drugs combined with pembrolizumab (an immunotherapy) and sometimes chemotherapy for advanced or metastatic esophageal cancer. It is for patients with a specific type of esophageal cancer (squamous cell carcinoma) that has spread and cannot be fully removed by surgery, and who have not received prior treatment for this advanced stage.

Why is this trial significant?

This trial addresses a critical need for more effective first-line treatments for advanced esophageal squamous cell carcinoma, a cancer with limited options and poor outcomes.

What are the potential risks of participating in NCT06780111?

Common side effects may include fatigue, nausea, diarrhea, and skin reactions. More serious risks can involve severe allergic reactions, lung inflammation (pneumonitis), heart problems, or damage to the eyes. Some treatments may affect your immune system's ability to fight infections. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06780111?

Ask your doctor about the specific investigational drugs being tested, potential side effects, and how this trial treatment compares to standard options. Be prepared for regular clinic visits for infusions, blood tests, scans to check your cancer, and to report any new symptoms or side effects promptly. Understand that you may be randomly assigned to receive different combinations of the study drugs. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06780111 signal from an investment perspective?

This trial, sponsored by Merck, explores novel combinations for a specific cancer type, indicating a focus on expanding the utility of pembrolizumab and potentially introducing new targeted therapies This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participation involves receiving study treatments and regular medical check-ups to monitor for side effects and cancer response. Alternatives may include standard chemotherapy or immunotherapy regimens. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

Related Conditions

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.