None listed
Conditions
Interventions
Pembrolizuma drug solution 400 mg for IV infusion every 6 weeks plus Lenvatinib drug capsule 8 mg (induction) / 14 mg (consolidation) orally once daily in combination with chemotherapy CAPOX or mFOLFOX6* [CAPOX: Capecitabine, drug tablet, 1000 mg/m2 BID for 14 days every 3 weeks orally plus Oxaliplatin, solution 130 mg/m2 for IV infusion every 3 weeks
mFOLFOX6:
Oxaliplatin solution 85 mg/m2 for IV infusion every 2 weeks in combination with 5-FU solution 400 mg/m2 IV bolus infusion plus 24
Chemotherapy CAPOX or mFOLFOX6*
[CAPOX: Capecitabine, drug tablet, 1000 mg/m2 BID for 14 days every 3 weeks orally plus oxaliplatin, solution 130 mg/m2 for IV infusion every 3 weeks
mFOLFOX6:
Oxaliplatin solution 85 mg/m2 for IV infusion every 2 weeks in combination with 5-FU solution 400 mg/m2 IV bolus infusion plus 2400 mg/m2 IV continuous infusion every 2 weeks plus Leucovorin solution 400 mg/m2 (or 200 mg/m2 for levoleucovorin) for IV infusion every 2 weeks]
Sponsors
Merck Sharp & Dohme Corp., una subsidiaria de Merck & Co. Inc.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 negative gastric or GEJ adenocarcinoma based on Siewert classification 1-3 [Mariette, C., et al 2011]. 2. Is not expected to require tumor resection during the treatment course. 3. Is HER2-negative per CAP/ASCP/ASCO guidance, by local/central testing. 4. Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator/radiology assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since the completion of radiation (by scans with contrast). 5. Is male or female at least 18 years of age inclusive, at the time of signing the informed consent. 6. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy, whichever comes last: • Refrain from donating sperm PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle OR • Must agree to use contraception as detailed below unless confirmed to be azoospermic. 7. 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. 8. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. 9. Has a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of study treatment. 10. Has provided a tumor tissue sample for PD-L1 and MSI biomarker analysis. In addition, the PD-L1 result must be determined as positive or negative, before randomization. 11. Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. 12. Has adequate organ function as defined in the following table (Table 3, see Protocol). Specimens must be collected within 10 days prior to the start of study intervention. Please refer to the protocol for the more information. Please refer to the protocol for more information
Exclusion criteria
Exclusion criteria: 1. Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. 2. Has had major surgery within 28 days prior to first dose of study interventions. 3. Has had radiotherapy within 14 days of randomization. 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. 4. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 5. Has known CNS metastases and/or carcinomatous meningitis. 6. Has severe hypersensitivity (≥Grade 3) to treatment with an mAb or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products. 7. Has had an allogeneic tissue/solid organ transplant. 8. Has perforation risks or significant GI bleeding. 9. Has GI obstruction, poor oral intake (CAPOX patients), or difficulty in taking oral medication (CAPOX patients). G-tubes, J-tubes and nasogastric tubes will not be permitted for treatment administration of capecitabine. Participants with existing esophageal stent are not eligible. Also, participants with known gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that may affect the absorption of lenvatinib. 10. 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 coinhibitory TCR (eg, CTLA-4, OX40, CD137). 11. Has received prior therapy with anti-VEGF TKI or anti-VEGF mAb. 12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug. 13. 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. 14. 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, etc.) is not considered a form of systemic treatment and is allowed. 15. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. 16. Has inadequate cardiac function assessed as: • Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by a MUGA or ECHO. • QTcF value >470 msec for males and >480 msec for females (mean of 3 measurements corrected for HR using Fridericia´s formula). 17. Has proteinuria >1+ on urine dipstick/urine analysis, with UPC ≥1. 18. 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. 19. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis. 20. Has a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Descriptive summary statistics (eg, counts, percentages) Measure:Safety and Tolerability (Part 1) Timepoints:Since the first dose administered to a randomized subject from Part 1 until day 21. ; Outcome name:Kaplan-Meier. Measure:Overall Survival (OS) Timepoints:The primary analysis will be conducted approximately 28 months after first participant randomized. The final analysis will be conducted approximately 38 months after first participant randomized. ; Outcome name:Kaplan-Meier. Measure:Progression-free Survival (PFS) per RECIST 1.1 Assessed by BICR Timepoints:The primary analysis will be conducted approximately 22 months after first participant randomized. The final analysis will be conducted approximately 28 months after first participant randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:M&N method [Miettinen, O. and Nurminen, M. 1985] Measure:Objective Response (OR) per RECIST 1.1 by BICR Timepoints:The analysis will be conducted approximately 22 months after first participant randomized. ; Outcome name:Descriptively using Kaplan-Meier medians and quartiles. Measure:Duration of Response (DOR) per RECIST 1.1 by BICR Timepoints:After a participant randomized have a confirmed CR or PR until progression or death for any cause, whichever occurs first. ; Outcome name:M&N method [Miettinen, O. and Nurminen, M. 1985] Measure:Safety and Tolerability (Part 2) Timepoints:Since the first dose administered to a randomized subject from Part 2 until discontinuation or death for any cause, whichever occurs first | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, China, Colombia, France, Germany, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Korea South, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kindgdom, United States
Contacts
Public ContactNelva Garcia
MERCK SHARP & DOHME PERU S.R.L
Outcome results
None listed