HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 180 days 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 180 days 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; and b) QT interval calculated according to the Fridericia method (QTcF) value =480 msec (mean of 3 measurements corrected for heart rate using Fridericia’s formula). 10. Have provided tumor tissue sample deemed adequate for PD-L1 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
Exclusion criteria
Exclusion criteria: 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 without progression. 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. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. 4. Has a 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. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 6. Has an 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). 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 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. 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 be confirmed as negative, a serum pregnancy test will be required. 17. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare PFS between treatment groups To compare overall survival (OS) between treatment groups.;Secondary Objective: To compare Objective Response Rate (ORR) between treatment groups. To estimate Duration of Response (DOR), per RECIST 1.1 as assessed by BICR for each treatment group. To assess the safety and tolerability of pembrolizumab in combination with trastuzumab plus chemotherapy by proportion of adverse events (AEs);Primary end point(s): (FPS) The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first (OS) The time from randomization to death due to any cause;Timepoint(s) of evaluation of this end point: Primary end points are Progression-free Survival (PFS) and Overall survival (OS). -IA2: Timing: to be performed after ~ 542 PFS events have occurred AND ~ 9 months after last participant randomized. Primary purpose: efficacy analysis for PFS and OS. -IA3: Timing: to be performed when at least 18 months after the last participant has been randomized AND at least 606 PFS events have been observed. This is the final PFS analysis. Primary purpose: efficacy analysis for PFS and OS. Read in the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective Response: Complete response (CR) or partial response (PR) DOR: For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. - Adverse events - Discontinuation of study treatment due to AEs;Timepoint(s) of evaluation of this end point: Secondary efficacy Objective Response. - IA1: Timing: to be performed when ~ 260 participants have been followed up for ~ 8.5 months. Primary purpose: efficacy and futility analysis for ORR | — |
Countries
Australia, Brazil, Chile, China, France, Germany, Guatemala, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp &Dohme de España SA
Outcome results
None listed