Pembrolizumab plus Lenvatinib plus Chemotherapy for the Treatment of Advanced/Metastatic HER2 Negative Gastric/Gastroesophageal Junction Adenocarcinoma

JRCT ID: jRCT2051200127

Registered date:29/01/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced/Metastatic HER2 Negative Gastric/Gastroesophageal Junction Adenocarcinoma
• Date of first enrollment: 05/02/2021
• Target sample size: 120
• Countries of recruitment: Australia,Japan,China,Japan,Hong Kong,Japan,South Korea,Japan,Taiwan,Japan,Belgium,Japan,Germany,Japan,Spain,Japan,France,Japan,United Kingdom,Japan,Israel,Japan,Italy,Japan,Poland,Japan,Russia,Japan,Turkey,Japan,Argentina,Japan,Chile,Japan,Colombia,Japan,Guatemala,Japan,Peru,Japan,Canada,Japan,the United States,Japan,Ireland,Japan
• Study type: Interventional

Intervention(s)

Biological: Pembrolizumab
400 mg Q6W by IV infusion
Other Names:
MK-3475
Keytruda(R)

Biological: Lenvatinib
Administered PO QD, 8 mg induction/14 mg consolidation.
Other Names:
MK-7902
E7080

Drug: Oxaliplatin
130 mg/m^2 administered by IV infusion on Day 1 of Weeks 1 and 4 of each Q6W cycle as part of CAPOX chemotherapy, or 85 mg/m^2 administered by IV infusion on Day 1 and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.

Drug: Capecitabine
1000 mg/m^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.

Drug: Leucovorin
Administered by IV infusion at 400 mg/m^2 on Day 1, and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.

Drug: 5-FU
400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous IV infusion administered on Day 1, and Week 1, 3, 5, of each Q2W cycle as part of mFOLFOX6 chemotherapy.

Outcome(s)

Primary Outcome

Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Part 1: Number of Participants with Adverse Events (AEs)
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) >=1
Part 2: OS in All Participants
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
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants

Secondary Outcome

Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS >=1
Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
-Has had major surgery within 28 days prior to first dose of study interventions
-Has had radiotherapy within 14 days of randomization
-Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
-Has known CNS metastases and/or carcinomatous meningitis
-Has severe hypersensitivity (>=Grade 3) to treatment with an monoclonal antibody (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
-Has had an allogeneic tissue/solid organ transplant
-Has perforation risks or significant gastrointestinal (GI) bleeding
-Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
-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 T-cell receptor
-Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
-Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
-Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
-Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
-Has inadequate cardiac function
-Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
-Has poorly controlled diarrhea
-Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
-Has peripheral neuropathy >=Grade 2
-Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
-Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
-Has weight loss of >20% within the last 3 months

Exclude criteria

Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
-Has had major surgery within 28 days prior to first dose of study interventions
-Has had radiotherapy within 14 days of randomization
-Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
-Has known CNS metastases and/or carcinomatous meningitis
-Has severe hypersensitivity (>=Grade 3) to treatment with an monoclonal antibody (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
-Has had an allogeneic tissue/solid organ transplant
-Has perforation risks or significant gastrointestinal (GI) bleeding
-Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
-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 T-cell receptor
-Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
-Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
-Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
-Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
-Has inadequate cardiac function
-Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
-Has poorly controlled diarrhea
-Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
-Has peripheral neuropathy >=Grade 2
-Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
-Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
-Has weight loss of >20% within the last 3 months

Related Information

• Primary Sponsor: Koh Yasuhiro
• Secondary ID(s): NCT04662710