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-GB
- 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. If the ratio is <2.0 but the HER2 gene copy number is >6 the participant may be considered ISH-positive.
3. Have measurable disease as defined by RECIST 1.1 by scans with IV contrast 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:
a. Left ventricular ejection fraction (LVEF) = 55% as determined by MUGA scan or ECHO. Note: Participants with EF 50 to 54 may still be eligible with discussion with Sponsor AND after consultation with cardiology AND after being medically optimized; and
b. QT interval calculated according to the Fridericia method (QTcF) value =470 msec for males and =480 msec for females (mean of 3 measurements corrected for heart rate using Fridericia's formula).
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: 0
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 previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization and there was no evidence of progression within the timeframe.
2.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.
3.Has had radiotherapy within 14 days of randomization.
4.Known additional malignancy that is progressing or has required active treatment within the past 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
5.Known active CNS metastases and/or carcinomatous meningitis.
6.Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
7.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
8.Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
9.Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis).
10.Has an active infection requiring systemic therapy.
11. Has poorly controlled diarrhea (eg, watery stool, uncontrollable bowel movement with drugs, Grade = 2 and number of defecations, = 5/day).
12.Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
13.Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase, hearing impairment, etc.), 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. Participants with a contraindication to standard-of-care therapy should be excluded, ie:
• Participants with a history of a severe and unexpected reaction to a fluoropyrimidine-containing treatment
• Participants with severe dyspnea at rest related to advanced disease stage or oxygen-dependent complications
• Participants presenting with clinically significant dehydration should avoid a cisplatin-containing regimen.
• Participants with hypokalemia, hypomagnesemia, or hypocalcemia
• Participants with evidence of neutropenia should not be assigned to an oxaliplatin-containing regimen as recommended by the local package insert.
• Participants with severe leukopenia should not be assigned to acapecitabine-containing regimen.
14. Has peripheral neuropathy > Grade 1.
15. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
16. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation (see Appendix 3). If the urine test is positive or cannot
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