Etude : KEYNOTE 811 / MK-3475-811

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : KEYNOTE 811 / MK-3475-811

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Chimiothérapie / Immunothérapie / Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 22/10/2021
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase 3 randomisée comparant l’efficacité du pembrolizumab associé au trastuzumab et à une chimiothérapie par rapport au placébo associé au trastuzumab et à une chimiothérapie en première ligne de traitement chez des patients ayant un adénocarcinome de l’estomac ou de la jonction gastro-oesophagienne métastatique HER2 positif

Spécialité : Organes digestifs
Localisation : C15 - Tumeur maligne de l'oesophage

Spécialité : Organes digestifs
Localisation : C16 - Tumeur maligne de l'estomac
Informations complémentaires
Schéma : Brief Summary:
The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).

Detailed Description:
Pembrolizumab (200 mg) or placebo will be administered intravenously [IV] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m^2 5-fluorouracil [5-FU] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m^2 capecitabine administered orally twice daily [BID] on days 1-14 of each 3-week cycle and 130 mg/m^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine [CDHP], and potassium oxonate [Oxo]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m^2) administered IV on Day 1 each 3-week cycle.

Phase : III

Stade : Métastatique

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma
HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
Has measurable disease as defined by RECIST 1.1 as determined by the site investigator
Male participants must agree to use approved contraception
Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment
Has a life expectancy of greater than 6 months
Has adequate organ function

Critères de non-inclusion : Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
Has had radiotherapy within 14 days of randomization
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
Has an active infection requiring systemic therapy
Has poorly controlled diarrhea
Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has peripheral neuropathy > Grade 1
Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months after the last dose of trial treatment
Has active or clinically significant cardiac disease
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
Has had an allogeneic tissue/solid organ transplant
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
CHU de Rouen - 1 Rue de Germont - 76000 ROUEN

Investigateur :
Frederic DI FIORE

Patricia FOSSE
02 32 88 86 10 poste 64 462

Statut de l'essai : CLOS

MAJ : 22/10/2021