Advanced/Metastatic HER2 Negative Gastric/Gastroesophageal Junction Adenocarcinoma MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
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
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
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 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 (abstinent on a long-term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause): 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 - Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed 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 (with a failure rate of =65 years) ye
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. 4.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years 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, such as: -Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization -Has preexisting =Grade 3 GI or non-GI fistula -Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to randomization 9.Has GI obstruction, poor oral intake (CAPOX patients), or difficulty in taking oral medication (CAPOX patients) 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 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. Replacement therapy 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 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 known history of active TB (Mycobacterium tuberculosis) 21.Has an active infection requiring systemic therapy 22.Has poorly controlled diarrhea (eg, watery stool, uncontrollable bowel movement with supportive medication, Grade =2 and number of defecations, =5/day) 23.Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment 24.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the investigator. Participants with a contraindication to SOC therapy should be excluded based on the following: -Has a history of a GI condition or procedure that in the opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.Objective (Part 1): To evaluate the safety and tolerability of treatment with pembrolizumab plus lenvatinib plus chemotherapy. 2.Objective (Part 2): To compare the overall survival between treatment groups. 3.Objective (Part 2): To compare the progression-free survival between treatment groups. ;Secondary Objective: 1.Objective (Part 2): To compare objective response rate between treatment groups. 2.Objective (Part 2): To estimate duration of response, per RECIST 1.1 as assessed by blinded independent central review for each treatment group in participants with programmed cell death ligand 1 combined positive score =1 and in all participants. 3.Objective (Part 2): To evaluate the safety and tolerability of pembrolizumab plus lenvatinib plus chemotherapy versus chemotherapy. ;Primary end point(s): 1. Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) 2. Part 1: Number of Participants with Adverse Events (AEs) 3. Part 1: Number of Participants who Discontinued Study Treatment Due to an AE 4. Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1 5. Part 2: OS in All Participants 6. Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1 CPS =1 7. Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants;Timepoint(s) of evaluation of this end point: 1. Up to ~21 days 2. Up to ~25 months 3. Up to ~22 months 4. Up to ~38 months 5. Up to ~38 months 6. Up to ~28 months 7. Up to ~28 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1 2. Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants 3. Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1 4. Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants 5. Part 2: Number of Participants with AEs 6. Part 2: Number of Participants who Discontinued Study Treatment Due to an AE;Timepoint(s) of evaluation of this end point: 1. Up to ~22 months 2. Up to ~22 months 3. Up to ~22 months 4. Up to ~22 months 5. Up to ~25 months 6. Up to ~22 months | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, China, Colombia, France, Germany, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Republic of, Peru, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed