A Phase II Study of Pembrolizumab in Subjects with Gastric Cancer

Phase 1

• Conditions: Gastric cancer; MedDRA version: 20.0Level: 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: EUCTR2014-003574-16-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-02
• Study Completion: 2021-07-23
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 315

Inclusion Criteria

For potential subjects in Cohort 1 (3L+ cohort):
1. Have received, and progressed on, at least two prior chemotherapy regimens. For the purposes of this study, perioperative, neoadjuvant, adjuvant chemotherapy regimens will not count as a prior regimen, unless the patient progressed while receiving adjuvant therapy or within 6 months of receiving adjuvant treatment. The date of progression and how progression was determined must be known with documentation available confirming progression on or after treatment. Previous treatment regimens must have included a fluoropyridine and platinum doublet (as part of either a line oftherapy or adjuvant treatment.
2. Be HER-2/neu -, or, if HER2/neu +, must have previously received treatment with trastuzumab
For potential subjects in Cohorts 2 or 3 (1L cohorts):
3. Is HER2/neu –
4. Have not received prior systemic anti-cancer therapy for their metastatic or advanced gastric or gastroesophageal junction adenocarcinoma. For the purposes of this study, perioperative, neoadjuvant, adjuvant chemotherapy regimens will not count as a prior regimen, unless disease progression has occurred during or within 6 months of adjuvant chemotherapy.
For all potential subjects:
5. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for FBR. However, the subject may participate in the main trial without participating in FBR.
6. Be ¿¿18 years of age on day of signing informed consent.
7. Have histologically or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies.
8. Be willing to provide newly-obtained or archived tissue for PD-L1 biomarker analysis and, based on the adequacy of the tissue sample quality for assessment of PD-L1 status, have received notice of eligibility. Newly-obtained tissue will be from the stomach and/or gastroesophageal junction (endoscopic tumor biopsy) or a metastatic location IF obtained as part of normal clinical practice. Repeat samples may be required if adequate tissue is not provided.
9. Be PD-L1 positive, if the subject is being allocated to a cohort which, at the time of enrollment, is only enrolling PD-L1 positive subjects
10. Have measurable disease based on RECIST 1.1 as determined by central imaging vendor.
11. Have a performance status of 0 or 1 on the ECOG Performance Scale
within 3 days prior to the first dose of study therapy.
12. Life expectancy of at least 3 months.
13. Females of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 or 180 days after the last dose of study medication. Males 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. Duration will be determined when
the subject is assigned to treatment. Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
14. Demonstrate adequate organ function
15. Female subjects of childbearing potential should have a negative urine or serum
pregnancy test within 72 h 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 190
F.1.3 Elderly (>=65 y

Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:
1. Experienced weight loss > 10 % over 2 months prior to first dose of study therapy.
2. Has clinical evidence of ascites by physical exam.
3. 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 al device within 4 weeks of the first dose of treatment.
4. Has active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment.
5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids (prednisone 10 mg or equivalent) may be approved after consultation with the Sponsor.
6. Has had a prior anti-cancer mAb within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from AE due to agents administered more than 4 weeks earlier.
7. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from AE due to a previously administered agent.
8. Has a known additional malignancy that is progressing or requires active treatment
9. Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable, 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.
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. 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.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive children within the trial, starting with the screening visit through 120 or 180 which the subject would be assigned.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has a known history of HIV.
17. Has known chronic or acute Hepatitis B or C infection.
18. Has received a live vaccine within 30 days of planned start of study 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