metastatic or advanced inoperable Her-2 negative esophagogastric adenocarcinoma MedDRA version: 20.1 Level: PT Classification code 10062878 Term: Gastrooesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic or unresectable, histologically confirmed Her-2 negative (as assessed locally by a certified test) adenocarcinoma of the gastroesophageal junction (AEG I-III according to Sievert´s classification) or the stomach. 2. Adjuvant/neoadjuvant or perioperative chemotherapy or chemoradiotherapy must have been finished at least 6 months before start of the study intervention. 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 4. Ability for oral intake of the study drug. 5. Male/female* participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of esophagogastric adenocarcinoma will be enrolled in this study. *There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently. 6. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 6 months after the last dose of study intervention and refrain from donating sperm during this period. 7. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), 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 as given in Appendix 3 during the treatment period and for at least 6 months after the last dose of study intervention. 8. The participant provides written informed consent for the trial. 9. Have measurable or evaluable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 10. Have provided archival tumor tissue sample. FFPE tissue blocks are preferred to slides. 11. Have adequate organ function as defined in protocol. Specimens must be collected within 14 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to start of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 2. 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 (e.g., CTLA-4, OX 40, CD137) or with a PARP inhibitor, including Olaparib. 3. Has received prior systemic anti-cancer therapy for metastatic or locally advanced (irresectable) disease. A prior neoadjuvant or adjuvant chemotherapy is allowed 4. Persistent clinically relevant toxicities, CTCAE Grade > 2 caused by previous cancer treatment. 5. Has received prior radiotherapy within 2 weeks of 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-CNS disease. 6. Participant received colony-stimulating factors within 28 days prior to the first dose of study intervention 7. Participant is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption. 8. Major surgery within 2 weeks of starting study intervention and patients must have recovered from any effects of any major surgery. 9. Participant is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks. 10. Participant is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study. 11. Concomitant use of drugs inhibiting DPD activity 12. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator, or patients with congenital long QT syndrome. 13. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 14. 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. 15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 16. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not excluded. 17. Participant has MDS/AML 18. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously completely resected brain metastases may participate if there is no sign of progression for at least 4 weeks by repeat imaging clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. 19. Has severe hypersensitivity (= Grade 3) to FOLFOX or CAPOX-based chemotherapy, olaparib, pembrolizumab and/or any of its excipients. 20. Known DPD deficiency. Patients with a reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of overall survival (OS) at one year ;Secondary Objective: Assessment of progression-free survival (PFS) Assessment of Objective response rate (ORR) Assessment of Best Overall Response (BOR) Assessment of Time to tumor progression (TTP) Assessment of Overall Survival (OS) Assessment of Feasibility Assessment of Safety and toxicity ;Primary end point(s): OS rate at 1 year;Timepoint(s) of evaluation of this end point: One year after inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS – time from enrollment to disease progression according to RECIST 1.1 and iRECIST or death due to any cause. ORR – percentage of patients with complete response (CR) or partial response (PR) according to RECIST 1.1 and iRECIST BOR – best response recorded from enrollment to treatment discontinuation for any reason TTP - time from enrollment to disease progression according to RECIST 1.1 and iRECIST. OS - time from enrollment to the date of death of any cause. Feasibility rate - severe toxicity/withdrawal rate before the fourth cycle of pembrolizumab/olaparib has been completed (Serious) Adverse Events - Recorded and graded according to NCI-CTC V5.0. Occurrence of (Serious) Adverse Events at any time during the study. Description by nature (Primary System Organ Class and Preferred Term), severity and causal relationship to drug administration;Timepoint(s) of evaluation of this end point: PFS, TTP, OS, toxicity: continuously ORR, BOR: at week 12 and then every 9 weeks Feasibility: after 4 cycles of pembrolizumab/olaparib | — |
Countries
Germany
Contacts
Public ContactIKF
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
Outcome results
None listed