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NCT06469944Recrutement en cours

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)

Résumé

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.

Critères d'inclusion

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

Critères d'exclusion

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 interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening • Has an active infection requiring systemic therapy • Has concurrent active hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] Ab positive and detectable HCV ribonucleic acid \[RNA\] infection or a known history of hepatitis B and/or C infection • Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study • Has gastrointestinal (GI) obstruction, poor oral intake, or difficulty in taking oral medication • Has poorly controlled diarrhea • Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention • Has history of allogeneic tissue/solid organ transplant • Has not adequately recovered from major surgery or has ongoing surgical complications

Contacts

Les coordonnées de l'équipe de l'essai s'affichent sur demande.

Voir la fiche officielle de l'essai
Statut
Recrutement en cours
Phase
Phase 1 · Phase 2
Type d'étude
Interventionnelle
Pays
Suisse, France, Allemagne, Italie, États-Unis, Brésil, Chili, Chine, Norvège, Corée du Sud, Taïwan, Thaïlande
Promoteur
Merck Sharp & Dohme LLC(Industrie)
N° de protocole
3475-06C
Pathologies
Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer
Interventions
Biologique, Médicament

Traitements évalués

  • Pembrolizumab
  • Sacituzumab Tirumotecan (sac-TMT)
  • Capecitabine
  • Leucovorin
  • Levoleucovorin
  • 5-Fluorouracil (5-FU)
  • Oxaliplatin
  • Patritumab Deruxtecan

Lieux · 46

  • Geneva, SuisseHôpitaux Universitaires de Genève (HUG) ( Site 6701)Recrute dans ce centre
  • Chur, SuisseKantonsspital Graubünden-Medizin ( Site 6700)Recrute dans ce centre
  • Brest, FranceCHU-BREST Cavale Blanche ( Site 5104)Recrute dans ce centre
  • Lille, FranceCIC. ( Site 5100)Recrute dans ce centre
  • Paris, FrancePitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 5102)Recrute dans ce centre
  • Heidelberg, AllemagneNCT-Department of Medical Oncology ( Site 6809)Recrute dans ce centre
  • Erdgeschoss, AllemagneHOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 6807)Recrute dans ce centre
  • Düsseldorf, AllemagneUniversitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802)Recrute dans ce centre
  • Meldola, ItalieIRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 5207)Recrute dans ce centre
  • Milan, ItalieFondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 5200)Recrute dans ce centre
  • Pisa, ItalieAzienda Ospedaliero Universitaria Pisana ( Site 5206)Recrute dans ce centre
  • Milan, ItalieOspedale San Raffaele-Oncologia Medica ( Site 5202)Recrute dans ce centre
  • Tucson, États-UnisUniversity of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927)Recrute dans ce centre
  • Los Angeles, États-UnisUCLA Hematology/Oncology - Santa Monica ( Site 6905)Recrute dans ce centre
  • Grand Rapids, États-UnisThe Cancer and Hematology Centers ( Site 6912)Recrute dans ce centre
  • East Syracuse, États-UnisHematology-Oncology Associates of Central NY, P.C. ( Site 6925)Recrute dans ce centre
  • Pittsburgh, États-UnisUPMC Hillman Cancer Center-UPMC ( Site 6904)Recrute dans ce centre
  • Houston, États-UnisUniversity of Texas MD Anderson Cancer Center ( Site 6920)Recrute dans ce centre
  • Natal, BrésilLiga Norte Riograndense Contra o Câncer ( Site 6303)Recrute dans ce centre
  • Porto Alegre, BrésilHospital Nossa Senhora da Conceição ( Site 6301)Recrute dans ce centre
  • São Paulo, BrésilICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300)Recrute dans ce centre
  • São Paulo, BrésilIBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304)Recrute dans ce centre
  • Port Montt, ChiliClínica Puerto Montt ( Site 6409)Recrute dans ce centre
  • Santiago, ChiliFALP-UIDO ( Site 6400)Recrute dans ce centre
  • Santiago, ChiliCentro de Oncología de Precisión-Oncology ( Site 6404)Recrute dans ce centre
  • Santiago, ChiliClínica UC San Carlos de Apoquindo ( Site 6405)Recrute dans ce centre
  • Santiago, ChiliBradfordhill-Clinical Area ( Site 6401)Recrute dans ce centre
  • Antofagasta, ChiliBradford Hill Norte ( Site 6407)Recrute dans ce centre
  • Beijing, ChineBeijing Cancer hospital-Digestive Oncology ( Site 5500)Recrute dans ce centre
  • Fuzhou, ChineThe 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501)Recrute dans ce centre

Au total, dans le monde, 46 des 50 centres listés au registre recrutent ; les 4 autres ne recrutent pas actuellement.

Statut par centre selon le registre ClinicalTrials.gov (dernière mise à jour publiée : 7 octobre 2026).

Ce statut peut avoir changé et ne dit rien de votre éligibilité : avant toute démarche, vérifiez avec votre oncologue ou le centre.

+ 16 autres lieux

Autres identifiants

  • MK-3475-06C · autre identifiant
  • KEYMAKER-06C · autre identifiant
  • 2023-509307-33-00 · autre registre
  • U1111-1299-8084 · autre registre
  • 2023 · financement NIH

Voir aussi

Autres versions

Ces résultats sont indicatifs et ne remplacent pas un avis médical — à discuter avec votre médecin.