A Phase III Study of Pembrolizumab in Subjects with Gastric Cancer

Phase 1

• Conditions: Gastric or Gastroesophageal Junction Adenocarcinoma; MedDRA version: 17.1Level: PTClassification code 10001150Term: Adenocarcinoma gastricSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005241-45-IT
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-26
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 720

Inclusion Criteria

1. Be willing and able to provide written informed consent/assent. The subject may also provide consent for FBR. However, the subject may participate in the main trial without participating in FBR.
2. Be = 18 years of age on day of signing informed consent
3. Have histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
4. Have metastatic disease or locally advanced, unresectable disease.
5. Have measurable disease as defined by RECIST 1.1 as determined by investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Have a performance status of 0 or 1 on the ECOG Performance Scale.
7. Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
a. To be considered as second-line, the subject needs to have the documentation of disease progression on first-line treatment. The disease progression can be confirmed by CT scan or by clinical evidence (such as cytology report from newly developed ascites and plural effusion).
b. Any new or worsening malignant effusion (documented by ultrasound) may be confirmed by pathologic criteria (histology and/or cytology) if appropriate.
c. A subject experiencing clinical disease progression during or within 6 months following the last dose of adjuvant therapy will be eligible for enrollment provided they received a platinum/fluoropyrimidine doublet as required.
d. To be eligible, the subject is required to have received at least one dose of platinum and fluoropyrimidine therapy.
8. Be willing to provide tissue for PD-L1 biomarker analysis and, based on the adequacy of the tissue sample quality for assessment of PD-L1 status, received permission for enrollment from the Core Lab. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
9. Subjects with HER-2/neu - tumors are eligible. For subjects with HER2/neu positive tumors or have an unknown tumor status, need to match the following:
a. If HER2/neu+ , subject must have documentation of disease progression on treatment containing trastuzumab.
b. Subjects with unknown status must have their HER2/neu status determined locally. If HER2/neu -, the subject will be eligible. If HER2/neu +, the subject must have documentation of disease progression on treatment containing trastuzumab.
10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity during study through 120 or 180 days after the last dose of study medication
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 or 180 days after the last dose of study therapy.
11. Demonstrate adequate organ function
12. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.

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 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device < 4 weeks of the first dose of treatment.
2. Has squamous cell or undifferentiated gastric cancer.
3. Has active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy < 7 days prior to the first dose of trial treatment
5. Has had a prior anti-cancer mAb < 4 weeks prior to Day 1 or has not recovered (i.e., = Grade 1 or at baseline) from AEs due to agents administered > 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy < 2 weeks prior to Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from AEs due to a previously administered agent.
7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
8. Has known CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
9. Has history or evidence of interstitial lung disease or active non-infectious pneumonitis.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
14. Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participated in Merck pembrolizumab (MK-3475) clinical trials.
15. Has a known history of HIV (HIV 1/2 antibodies).
16. Has known active Hepatitis B (e.g., HBsAg reactive) or C.
17. Has received a live vaccine within 30 days of planned start of study therapy.
18. Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
19. Is or has an immediate family member who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified