A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma): Substudy 06C

New combination therapy for advanced stomach and esophageal cancer

NCT: NCT06469944 · Status: RECRUITING · Phase: Phase 2 · Sponsor: Merck Sharp & Dohme LLC · Started: 2024-09-20 · Est. Completion: 2029-09-12

Plain English Summary

Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06) is a Phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC studying Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer. This study tests new drug combinations, including pembrolizumab (an immunotherapy), chemotherapy, and other investigational agents, for advanced stomach, gastroesophageal junction, or esophageal cancer. It is for patients with newly diagnosed, advanced, and unresectable or metastatic forms of these cancers who have not received prior treatment. Participation involves receiving the study drugs and regular medical check-ups, including imaging and blood tests, to monitor for side effects and treatment response. Standard chemotherapy or other approved treatments for advanced gastroesophageal cancer are the current alternatives. The trial aims to enroll 160 participants.

Official Summary

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with newly diagnosed, advanced, unresectable, or metastatic stomach, gastroesophageal junction, or esophageal adenocarcinoma. Must have tumors that are HER2-negative and have not been previously treated for advanced disease. Patients must be in good general health with adequate organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Individuals with certain pre-existing conditions like active inflammatory bowel disease, uncontrolled cardiovascular disease, or active autoimmune disease may not be eligible. This trial is studying Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine how safe the new drug combinations are and how well they shrink tumors, indicating their potential to control the cancer's growth. The specific primary outcome measures are: Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) (Up to approximately 28 days); Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE) (Up to approximately 28 days); Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE (Up to approximately 28 days); Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) (Up to approximately 28 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 gastroesophageal cancers, aiming to improve outcomes for patients with limited options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer, where improved treatment options are needed.

Investor Insight

This trial, sponsored by Merck, is investigating novel combinations for a significant cancer market, suggesting potential for new treatment standards if successful, though approval probability depends 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 they might interact with your current health. Participation involves regular clinic visits for drug infusions, blood draws, scans to check cancer progress, and monitoring for any adverse reactions. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team promptly. 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 and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line (1L) gastroesophageal adenocarcinoma
* Is not expected to require tumor resection during the treatment course
* Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
* Core/excisional biopsy of a tumor lesion not previously irradiated has been provided
* Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
* Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible
* Has adequate organ function
* Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blinded independent central review (BICR)
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the first dose of study intervention
* Has a life expectancy of at least 6 months
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation/randomization
* Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy

Exclusion Criteria:

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

* Has squamous cell or undifferentiated gastroesophageal cancer.
* Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma
* Has experienced weight loss \>20% over 3 months before the first dose of study intervention
* Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has Grade ≥2 peripheral neuropathy
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
* Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
* Has history of human immunodeficiency virus (HIV) infection with Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor receptor 3 (HER3) targeted agents
* Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC) and/or a topoisomerase I inhibitor-based chemotherapy
* Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
* Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)
* 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
* Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy 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 Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, patritumab deruxtecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Has history of (noninfectious) pneumonitis or interstitial lung disease (ILD) that required steroids or has current pneumonitis or ILD, or where suspected ILD or pneumonitis cannot be ruled out by ima

Trial Locations

Frequently Asked Questions

What is clinical trial NCT06469944?

NCT06469944 is a Phase 2 INTERVENTIONAL study titled "Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)." It is currently recruiting and is sponsored by Merck Sharp & Dohme LLC. The trial targets enrollment of 160 participants.

What conditions does NCT06469944 study?

This trial investigates treatments for Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer. The primary condition under study is Gastroesophageal Junction.

What treatments are being tested in NCT06469944?

The interventions being studied include: Pembrolizumab (BIOLOGICAL), Sacituzumab Tirumotecan (sac-TMT) (BIOLOGICAL), Capecitabine (DRUG), Leucovorin (DRUG), Levoleucovorin (DRUG). Administered via intravenous (IV) infusion.

What does Phase 2 mean for NCT06469944?

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 NCT06469944?

This trial is currently "Recruiting." It started on 2024-09-20. The estimated completion date is 2029-09-12.

Who is sponsoring NCT06469944?

NCT06469944 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 NCT06469944?

The trial aims to enroll 160 participants. The trial is currently recruiting and accepting new participants.

How is NCT06469944 designed?

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

What are the primary outcomes being measured in NCT06469944?

The primary outcome measures are: Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) (Up to approximately 28 days); Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE) (Up to approximately 28 days); Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE (Up to approximately 28 days); Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) (Up to approximately 28 months). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06469944 being conducted?

This trial is being conducted at 20 sites, including Tucson, Arizona; Los Angeles, California; Louisville, Kentucky; Grand Rapids, Michigan and 16 more sites (United States, Brazil, Chile).

Where can I find official information about NCT06469944?

The official record for NCT06469944 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06469944. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06469944 testing in simple terms?

This study tests new drug combinations, including pembrolizumab (an immunotherapy), chemotherapy, and other investigational agents, for advanced stomach, gastroesophageal junction, or esophageal cancer. It is for patients with newly diagnosed, advanced, and unresectable or metastatic forms of these cancers who have not received prior treatment.

Why is this trial significant?

This trial addresses a critical need for more effective first-line treatments for advanced gastroesophageal cancers, aiming to improve outcomes for patients with limited options.

What are the potential risks of participating in NCT06469944?

Common side effects may include fatigue, nausea, diarrhea, and skin reactions. More serious risks can involve immune system reactions, lung inflammation, or problems with blood counts. Specific risks related to the investigational drugs, such as potential liver or kidney issues, will be closely monitored. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06469944?

Ask your doctor about the specific investigational drugs being tested, potential side effects, and how they might interact with your current health. Participation involves regular clinic visits for drug infusions, blood draws, scans to check cancer progress, and monitoring for any adverse reactions. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team promptly. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06469944 signal from an investment perspective?

This trial, sponsored by Merck, is investigating novel combinations for a significant cancer market, suggesting potential for new treatment standards if successful, though approval probability depends 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 the study drugs and regular medical check-ups, including imaging and blood tests, to monitor for side effects and treatment response. 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.

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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.