Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)

NCT06780111
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
298
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2025-07-30
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Number of sites
52
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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.
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Short title
Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)
clinicaltrials.gov
Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2032-01-04
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First posted
2025-01-17
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Registry last updated
2026-10-27
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Primary completion date
2032-01-04
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Start date
2025-07-30
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Participants
298
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Participant count basis
Estimated
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Planned participants
298
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Protocol amendments
6
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Number of sites
52
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06780111
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ClinicalTrials.gov ID
NCT06780111
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase

    Timeframe: Up to approximately 28 days

    Percentage of participants experiencing toxicities that are possibly, probably, or definitely related to study intervention; that meet pre-defined severity criteria; and result in a change in the given dose.

  2. Percentage of Participants who Experience an Adverse Event (AE)

    Timeframe: Up to approximately 77 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.

  3. Objective Response Rate (ORR)

    Timeframe: Up to approximately 77 months

    ORR is defined as a confirmed complete response (CR: the disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR). The percentage of participants who experience CR or PR as assessed by BICR will be presented.

  1. Duration of Response (DOR)

    Timeframe: Up to approximately 77 months

    For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.

  2. Progression-Free Survival (PFS)

    Timeframe: Up to approximately 77 months

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.

  3. Overall Survival (OS)

    Timeframe: Up to approximately 77 months

    OS is defined as the time from allocation/randomization to death due to any cause.

  4. Disease Control Rate (DCR)

    Timeframe: Up to approximately 77 months

    DCR is defined as a confirmed complete response (CR) or partial response (PR), or stable disease (SD) with at least 6 months PFS per RECIST 1.1 as assessed by BICR.

  5. Maximum Plasma Concentration (Cmax) of I-DXd

    Timeframe: At designated time points up to approximately 65 months

    Cmax is defined as the peak level I-DXd reaches in the blood plasma. Blood samples collected predose and at multiple timepoints postdose will be used to determine the Cmax of I-DXd when co-administered with other investigational agents.

  6. Time to Maximum Plasma Concentration (Tmax) of I-DXd

    Timeframe: At designated time points up to approximately 65 months

    Tmax is defined as the time it took I-DXd to reach its peak level in blood plasma. Blood samples collected predose and at designated timepoints postdose will be used to determine the Tmax of I-DXd when co-administered with other investigational agents.

  7. Area Under the Concentration-Time Curve from Time 0 to Last Measurable Plasma Concentration (AUClast) of I-DXd

    Timeframe: At designated time points up to approximately 65 months

    AUClast is defined as the area under the concentration-time curve from time 0 to the last measurable concentration of I-DXd in the blood plasma. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUClast of I-DXd in combination with other agents.

  8. Area Under the Concentration-Time Curve from Time 0 to the End of the Dosing Period (AUCtau) of I-DXd

    Timeframe: At designated time points up to approximately 65 months

    AUCtau is defined as the area under the concentration-time curve from time zero to the end of the dosing period. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUCtau of I-DXd in combination with other agents.

  9. The Percentage of Participants with Antidrug Antibodies (ADA) Against I-DXd

    Timeframe: Up to approximately 65 months

    Blood samples collected at designated timepoints will be used to determine the ADA response to I-DXd. The percentage of participants with ADA will be reported.

  10. The Percentage of Participants with Treatment-Emergent ADA Against I-DXd

    Timeframe: Up to approximately 65 months

    Blood samples collected at designated timepoints will be used to determine the treatment-emergent ADA response to I-DXd. The percentage of participants who have treatment-emergent I-DXd ADA will be reported.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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 had AEs due to previous anticancer therapies that have recovered to ≤Grade 1 or baseline. Endocrine-related AEs that are adequately treated with hormone replacement are elegible.
  • 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.

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 by a 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 a history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), has a current diagnosis of ILD, or has clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out.
  • 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.
Sources for eligibility
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  • UPMC Hillman Cancer Center ( Site 1904)Pittsburgh, United StatesRecruiting
  • Liga Norte Riograndense Contra o Cancer ( Site 1301)Natal, BrazilRecruiting
  • Hospital Nossa Senhora da Conceicao ( Site 1300)Porto Alegre, BrazilRecruiting
  • IBCC - Instituto Brasileiro de Controle do Cancer ( Site 1303)São Paulo, BrazilRecruiting
  • ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1302)São Paulo, BrazilRecruiting
  • Clínica Puerto Montt ( Site 1406)Port Montt, ChileRecruiting
  • Fundación Arturo López Pérez ( Site 1400)Santiago, ChileRecruiting
  • Centro de Oncología de Precisión ( Site 1402)Santiago, ChileRecruiting
  • Clínica UC San Carlos de Apoquindo ( Site 1403)Santiago, ChileRecruiting
  • Bradfordhill ( Site 1401)Santiago, ChileRecruiting
  • Bradford Hill Norte ( Site 1405)Antofagasta, ChileRecruiting
  • The Second Affiliated Hospital of Anhui Medical University ( Site 9511)Hefei, ChinaRecruiting
  • Beijing Cancer Hospital ( Site 9500)Beijing, ChinaRecruiting
  • The First Affiliated Hospital of Xiamen University ( Site 9503)Xiamen, ChinaRecruiting
  • Henan Cancer Hospital ( Site 9509)Zhengzhou, ChinaRecruiting
  • Xuzhou Central Hospital ( Site 9512)Xuzhou, ChinaRecruiting
  • The First Affiliated Hospital of Nanchang University ( Site 9505)Nanchang, ChinaRecruiting
  • Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 9000)Brno, CzechiaRecruiting
  • C.H.R.U. de Brest - Hopital Cavale Blanche ( Site 9104)Brest, FranceRecruiting
  • CHU Lille - Institut Coeur Poumon ( Site 9100)Lille, FranceRecruiting
  • Pitie Salpetriere University Hospital ( Site 9102)Paris, FranceRecruiting
  • NCT-Department of Medical Oncology ( Site 1809)Heidelberg, GermanyRecruiting
  • HOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 1807)Erdgeschoss, GermanyRecruiting
  • Universitaetsklinikum Duesseldorf ( Site 1808)Düsseldorf, GermanyRecruiting
  • Universitätsklinikum Carl Gustav Carus - Medical Oncology ( Site 1806)Dresden, GermanyRecruiting

And 27 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • MK-3475-06E
  • U1111-1307-6484
  • 2024-514273-22-00
  • jRCT2041240166
Sources for references
clinicaltrials.gov

Related records

Drugs (6)

Collaborators (1)

Lead sponsors (1)

Conditions (1)

Targets (3)