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: 21.0Level: LLTClassification code 10058526Term: Oesophageal adenocarcinoma metastaticSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001757-27-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
- 1542
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 with an average HER2 copy number <4.0 signals/cell). 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. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days after
the last dose of chemotherapy:
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and
usual lifestyle (abstinent on a long-term and persistent basis) and agree
to remain abstinent
OR
Must agree to use contraception unless confirmed to be azoospermic
(vasectomized or secondary to medical cause) as detailed below:
• Agree to use a male condom plus partner use of an additional
contraceptive method when having penile-vaginal intercourse with a
WOCBP who is not currently pregnant.
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
female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective
(with a failure rate of <1% per year), with low user dependency, or be
abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis), during the
intervention period and for at least 180 days after the last dose of
chemotherapy or 120 days after the last dose of pembrolizumab,
whichever is last, and agrees not to donate eggs (ova, oocytes) to others
or freeze/store for her own use for the purpose of reproduction during
this period. The investigator should evaluate the potential for
contraceptive method failure (ie, noncompliance, recently initiated) in
relationship to the first dose of study intervention.
- A WOCBP must have a negative highly sensitive pregnancy test ([urine
or serum] as required by local regulations) within 24 hours before the first dose of study intervention.
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. Formalinfixed, 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
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.
5. Has had previous therapy for locally advanced, unresectable and/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 PDL2 agent or with an agent directed to another stimulatory or coinhibitory 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 or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines is 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 required steroidsor has current pneumonitis.
17. Has an active infection requiring systemic therapy.
18. Has a known history of human immunodeficiency virus (HIV)infection.
19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined asHCV RNA [qualitative] is detected) infection.
20. Has a known history of active tuberculosis.
Please refer to the Protocol for the remaining exclusio
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