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 (KEYNOTE 811)
- Conditions
- HER2 Positive Advanced Gastric or Gastroesophageal Junction AdenocarcinomaMedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000224-34-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 732
1. Male/female participants who are at least 18 years of age on the day of signing the informed consent with histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive
gastric or GEJ adenocarcinoma.
2. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH), as assessed by central review on primary or metastatic tumor. ISH positivity is defined as a ratio of = 2.0 for the number of HER2 gene copies to the number of
signals for CEP17.
3. Have measurable disease as defined by RECIST 1.1 as determined by the site investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Note: The exact same image acquisition and processing parameters should be used throughout the study.
4. A male participant must agree to use an adequate method of contraception as outlined in Appendix 3 of the Protocol, for the course of the study through 7 months after the last dose of all study treatments.
5. A female participant is eligible to participate if she is not pregnant (see Appendix 3 of the Protocol), not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment.
6. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main study without participating in Future Biomedical Research.
7. Have a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of trial treatment.
8. Have a life expectancy of greater than 6 months.
9. Participants must have a 12-lead electrocardiogram (ECG) and echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed by the investigator or other qualified person to evaluate cardiac function prior to enrollment in the study.
Adequate cardiac function will be assessed by: Left ventricular ejection fraction (LVEF) >= 55% as determined by MUGA scan or ECHO. Note: Participants with EF 40 to 54 may still be eligible with discussion with Sponsor AND after consultation with cardiology AND after being medically optimized.
10. Have provided tumor tissue sample deemed adequate for PD-L1 and MSI biomarker analysis. The PD-L1 result must be determined as positive or negative.
11. Have adequate organ function as defined in the Table 2 in the Protocol. Specimens must be collected within 10 days prior to the start of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 366
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 366
1.Has had prev ther for local adv 1resect or metast gastric/GEJcancer.Particip may have receivedprior neoadjuvant or adjuv ther aslongas it was completed at least6months prior to randomiz w/o progres.2.Has had major surgery,open biopsy or signif traum injury within28days prior to randomiz,or anticip of theneed for major surgery during the course of stu treat.3.Has had radiother within14days of randomiz.Particip must have recov from all radiation-related tox,not require corticost,and not have had radiation pneumonitis.A1-week washout is permitted for palliative radiation to non-CNSdisease.4.Has a known addit malignancy that is progress or has required active treat withinthe past5years.Exceptionsinclude basalcellcarcinomaoftheskin,squamouscellcarcinomaofthe skin that has 1dergone potentially curative ther or insitucervicalcancer.5.Has known active CNSmetastases and/orcarcinomatous meningitis.Particip with prevly treated brain metastases may particip provided they are radiologically stable,ie,w/oevidence of progress foratleast4weeks by repeat imaging(perform during screening),clinically stable and w/orequirement of steroidtreat for atleast14days prior to first dose of stu treat.6.Has an active autoimmdisease that has required systemic treat inpast2years.Replacem ther is not consid a form of systemic treat and is allowed.7.Has a diagn of imm1odef or is receiving chronic systemic steroid ther(in dosing>10mgdaily ofprednisone equiv)or any other form of imm1osupp ther within7days prior the first dose of trial drug.8.Has a hist of(non-infect)pneumonitis that required steroids or curr pneumonitis.9.Has a known hist of active tuberculosis.Notesting for TB is required 1less mandated by local health authority.10. Has an active infection requiring systemic ther.11.Has poorly controll diarrhea(eg,watery stool,1controllable bowel movement with drugs,Grade=2and numb ofdefecations,=5/day).12.Accum of pleural,ascitic,or pericardial fluid requiring drainage within2weeks prior to enrollment.If the particip is receiving diuretic drugs for other reasons,it is acceptable.13.Has a hist or curr evid of any condition,ther,or lab abnormality that might conf the results of the trial,interfere with theparticipant’s particip for the full duration of the trial,or is not in the best interest of the particip to particip,in theopinion of the investigator.Particip with a contraindic to standard-of-care therapy should be excluded.14.Has peripheral neuropathy>Grade1.15.Has a known psychiatric or substance abuse disorder that would interf with cooperation with the requirements of the trial.16.A WOCBP who has a+urine pregntest within72hours prior to randomiz or treat allocation(seeAppendix3).If the urine test is+or cannot be confirmed as negative,a serum pregn test will be required.17.Is pregnant or breastfeeding,or expecting to conceive or father children within the projected durat of the trial,starting withthe screening visit through7months after the last dose of trial treat.18.Has active or clinical signif cardiac disease.19.Has a known hist of HIV(HIV1/2ab).No testing for HIV is required 1less mandated by local health authority.20.Has a known hist of HepatB(HepatBsurface antigen reactive)or known active HepatCvirus(HCVRNA qualitative is detected)infection.No testing for HepatB and HepatC is required 1less mandated bylocal health authority.21.Has severe hypersensitivity(>=Grade 3)to pembroliz,trastuz,stu chemotherapy agents and/or to any excipients,murine prot,or platinu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method