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NCT06445972Recrutement en cours

Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

Résumé

This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, and HER3-DXD plus ramucirumab versus ramucirumab plus paclitaxel for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Critères d'inclusion

The main inclusion criteria include but are not limited to the following: • Has histologically and/or cytologically confirmed diagnosis of previously treated, second line (2L) (received first line (1L) treatment) gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma • Has metastatic disease or locally advanced, unresectable disease • Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy • Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines • Can provide a core/excisional biopsy of a tumor lesion not previously irradiated (collected from a biopsy performed after the most recent systemic anticancer therapy regimen) • AEs due to previous anticancer therapies must be ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable • Has Eastern Cooperative Oncology Group performance status of 0 or 1 • Has a life expectancy of at least 3 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 experienced weight loss \>20% over 3 months before the first dose of study intervention • Has 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 a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to allocation/randomization • Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea) • Has uncontrolled, significant cardiovascular disease or cerebrovascular disease • Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to allocation/randomization • Has uncontrolled arterial hypertension ≥150/≥90 mm mercury (Hg) • Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment • Has undergone major surgery within 28 days prior to allocation/randomization, or central venous access device placement within 7 days prior to allocation/randomization or planned major surgery following initiation of study treatment • Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents • Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents • Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to allocation/randomization • Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry • Has history of GI perforation and/or fistulae within 6 months prior to allocation/randomization • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease • Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or HER3-targeted agent, topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy, or any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways • Has received prior systemic anticancer therapy 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 received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration • Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded • Has known active central nervous system metastases and/or carcinomatous meningitis • Has an active infection requiring systemic therapy • Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid) infection • History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, or where suspected ILD or pneumonitis cannot be ruled out by imaging at screening • Has severe hypersensitivity (Grade ≥3) to MK-2870, or HER3-DXd, any of their excipients, and/or to another biologic therapy • Has not adequately recovered from major surgery or have 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
Promoteur
Merck Sharp & Dohme LLC(Industrie)
N° de protocole
3475-06D
Pathologies
Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer
Interventions
Biologique, Médicament

Traitements évalués

  • Ramucirumab
  • Paclitaxel
  • Sacituzumab Tirumotecan
  • Rescue Medications
  • HER3-DXd

Collaborateurs

Daiichi Sankyo

Lieux · 44

  • Geneva, SuisseHôpitaux Universitaires de Genève (HUG) ( Site 8701)Recrute dans ce centre
  • Chur, SuisseKantonsspital Graubünden-Medizin ( Site 8700)Recrute dans ce centre
  • Brest, FranceCentre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi ( Site 7104)Recrute dans ce centre
  • Lille, FranceCIC. ( Site 7100)Recrute dans ce centre
  • Paris, FrancePitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 7102)Recrute dans ce centre
  • Heidelberg, AllemagneNCT-Department of Medical Oncology ( Site 8809)Recrute dans ce centre
  • Erdgeschoss, AllemagneHOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 8807)Recrute dans ce centre
  • Düsseldorf, AllemagneUniversitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 8802)Recrute dans ce centre
  • Meldola, ItalieIRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 7207)Recrute dans ce centre
  • Milan, ItalieFondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 7200)Recrute dans ce centre
  • Pisa, ItalieAzienda Ospedaliero Universitaria Pisana ( Site 7206)Recrute dans ce centre
  • Milan, ItalieOspedale San Raffaele-Oncologia Medica ( Site 7202)Recrute dans ce centre
  • Tucson, États-UnisUniversity of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927)Recrute dans ce centre
  • Los Angeles, États-UnisUCLA Hematology/Oncology - Santa Monica ( Site 8905)Recrute dans ce centre
  • Grand Rapids, États-UnisThe Cancer and Hematology Centers ( Site 8912)Recrute dans ce centre
  • East Syracuse, États-UnisHematology-Oncology Associates of Central NY, P.C. ( Site 8925)Recrute dans ce centre
  • Pittsburgh, États-UnisUPMC Hillman Cancer Center-UPMC ( Site 8904)Recrute dans ce centre
  • Houston, États-UnisUniversity of Texas MD Anderson Cancer Center ( Site 8920)Recrute dans ce centre
  • Natal, BrésilLiga Norte Riograndense Contra o Câncer ( Site 8303)Recrute dans ce centre
  • Porto Alegre, BrésilHospital Nossa Senhora da Conceição ( Site 8301)Recrute dans ce centre
  • São Paulo, BrésilIBCC - Instituto Brasileiro de Controle do Câncer ( Site 8304)Recrute dans ce centre
  • São Paulo, BrésilICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 8300)Recrute dans ce centre
  • Port Montt, ChiliClínica Puerto Montt ( Site 8409)Recrute dans ce centre
  • Talca, ChiliCentro de Investigación del Maule ( Site 8408)Recrute dans ce centre
  • Santiago, ChiliFALP-UIDO ( Site 8400)Recrute dans ce centre
  • Santiago, ChiliCentro de Oncología de Precisión-Oncology ( Site 8404)Recrute dans ce centre
  • Santiago, ChiliClínica UC San Carlos de Apoquindo ( Site 8405)Recrute dans ce centre
  • Santiago, ChiliBradfordhill-Clinical Area ( Site 8401)Recrute dans ce centre
  • Antofagasta, ChiliBradford Hill Norte ( Site 8407)Recrute dans ce centre
  • Beijing, ChineBeijing Cancer hospital-Digestive Oncology ( Site 7500)Recrute dans ce centre

Au total, dans le monde, 44 des 46 centres listés au registre recrutent ; les 2 autres ne recrutent pas actuellement.

Statut par centre selon le registre ClinicalTrials.gov (dernière mise à jour publiée : 3 septembre 2026).

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

+ 14 autres lieux

Autres identifiants

  • 2023-509306-29-00 · autre registre
  • U1111-1299-8160 · autre registre
  • MK-3475-06D · autre identifiant
  • 2023 · financement NIH

Voir aussi

Autres versions

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