Pembrolizumab/placebo plus chemotherapy as first-line therapy in participants with HER2 negative advanced gastric or GEJ adenocarcinoma
- Conditions
- HER2 negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinomaMedDRA version: 20.0Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10058526Term: Oesophageal adenocarcinoma metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001757-27-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 780
1. Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, with known PD-L1 expression status.
2. Has HER2 negative cancer. HER2 negative is defined as: IHC (0, or 1+) or fluorescence in situ hybridization (FISH) negative (HER2:CEP17 ratio <2). FISH can be replaced with locally available in situ hybridization (ISH) methods acceptable as per institutional guidelines (eg, DISH).
3. Is Male or Female.
4. Is at least 18 years of age at the time of signing the informed consent (or acceptable age according to local regulations, whichever is older).
5. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater, and must refrain from donating sperm during this period.
6. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 5.
OR
b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
7. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. 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.
8. Has measurable disease per RECIST 1.1 as assessed by investigator assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
9. Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
10. Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis.
11. Has provided tumor tissue sample for MSI biomarker analysis.
12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 3 days prior to the start of study intervention).
13. Has adequate organ function, as defined in the protocol. Specimens must be collected within 10 days prior to the start-of-study intervention.
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 230
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 550
1. Has squamous cell or undifferentiated gastric cancer.
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 intervention.
3. Has pre-existing peripheral neuropathy >Grade 1.
4. Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
5. 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.
6. 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 (eg, CTLA-4, OX-40, CD137).
7. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization.
8. Has received prior radiotherapy within 2 weeks prior to start of study intervention. 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-central nervous system (CNS) disease.
9. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
10. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
11. 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 to the first dose of study intervention.
12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
13. 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 intervention.
14. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
15. 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) is not considered a form of systemic treatment and is allowed.
16. Has a history of (non-infectious) pneumonitis that requir
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