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KEYNOTE 811: A phase III, randomized, double-blind trial comparing trastuzumab plus chemotherapy and pembrolizumab with trastuzumab plus chemotherapy and placebo as first-line treatment in participants with HER2 positive advanced gastric or gastroesophageal junction adenocarcinoma

Description

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)..

Status

Accepting new patients

Primary Study Objective(s)

The study's objective is to evaluate:

  • Progression-free survival (PFS)
  • Overall survival (OS)

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have a histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma
  • Are 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
  • Have measurable disease as defined by RECIST 1.1 as determined by the site investigator
  • Are male and agree to use approved contraception
  • Are female and not pregnant or breastfeeding, and are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
  • Have 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
  • Have a life expectancy of greater than 6 months
  • Have adequate organ function

Excluding patients who:

  • Have had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
  • Have 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
  • Have had radiotherapy within 14 days of randomization
  • Have a known additional malignancy that is progressing or has required active treatment within the past 5 years
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Have an active autoimmune disease that has required systemic treatment in the past two years
  • Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy
  • Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Have a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
  • Have an active infection requiring systemic therapy
  • Have poorly controlled diarrhea
  • Have 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.
  • Have 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
  • Have peripheral neuropathy > Grade 1
  • Have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
  • Are a WOCBP who has had a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
  • Are 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
  • Have active or clinically significant cardiac disease
  • Have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Have 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
  • Have severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
  • Have had an allogeneic tissue/solid organ transplant
  • Have 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])