SACITUZUMAB TIRUMOTECAN for Gastroesophageal adenocarcinoma | Gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma | Esophageal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic 1L gastroesophageal adenocarcinoma\n- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation/randomization\n- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening\n- Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy\n- Is not expected to require tumor resection during the treatment course\n- Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines.\n- Core/excisional biopsy of a tumor lesion not previously irradiated has been provided\n- Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤ Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible\n- Has adequate organ function\n- Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blind independent review committee (BICR)\n- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 3 days before allocation/randomization\n- Has a life expectancy of at least 6 months"}

Exclusion criteria

• {"criterion_text":"- Has squamous cell or undifferentiated gastroesophageal cancer.\n- Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor (HER3) targeted agents.\n- Has received prior treatment with a topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy\n- Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention\n- Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)\n- Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids\n- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention\n- Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration\n- Has 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 intervention\n- Has known additional malignancy that is progressing or has required active treatment within the past 3 years\n- Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma\n- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis\n- Has Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, patritumab deruxtecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients\n- Has active autoimmune disease that has required systemic treatment in the past 2 years\n- Has history of (noninfectious) pneumonitis or interstitial lung disease (ILD) that required steroids or has current pneumonitis or ILD, or where suspected ILD or pneumonitis cannot be ruled out by imaging at screening\n- Has an active infection requiring systemic therapy\n- Has concurrent active hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) and/or hepatitis C (defined as anti-hepatitis C virus [HCV] Ab positive and detectable HCV ribonucleic acid [RNA] infection or a known history of hepatitis B and/or C infection\n- Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study\n- Has GI obstruction, poor oral intake, or difficulty in taking oral medication\n- Has poorly controlled diarrhea\n- Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention\n- Has experienced weight loss >20% over 3 months before the first dose of study intervention\n- Has history of allogeneic tissue/solid organ transplant\n- Have not adequately recovered from major surgery or have ongoing surgical complications\n- Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing\n- Has Grade >2 peripheral neuropathy\n- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease\n- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention\n- Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment\n- Has history of human immunodeficiency virus (HIV) infection"}

Primary endpoints

• {"endpoint_text":"- Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)","definition_or_measurement_approach":"Count of participants experiencing one or more DLTs during the Safety Lead-In Phase (DLT definition as per protocol; DLT occurrences used for dose-escalation/safety assessment)."}
• {"endpoint_text":"- Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)","definition_or_measurement_approach":"Count of participants with reported AEs during the Safety Lead-In Phase (per protocol AE reporting and grading)."}
• {"endpoint_text":"- Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE","definition_or_measurement_approach":"Count of participants who permanently discontinued study intervention because of an AE."}
• {"endpoint_text":"- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blind Independent Review Committee (BICR)","definition_or_measurement_approach":"ORR evaluated per RECIST 1.1 criteria as assessed by a blinded independent central review (BICR)."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR","definition_or_measurement_approach":"PFS measured per RECIST 1.1 as assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR","definition_or_measurement_approach":"DOR measured per RECIST 1.1 as assessed by BICR."}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"OS measured as time from allocation/randomization to death from any cause."}
• {"endpoint_text":"- Number of Participants Who Experience an Adverse Event (AE)","definition_or_measurement_approach":"Count/incidence of AEs reported during study treatment (per protocol safety reporting)."}
• {"endpoint_text":"- Number of Participants Who Discontinue Study Treatment Due to an AE","definition_or_measurement_approach":"Count of participants discontinuing study treatment because of AEs."}
• {"endpoint_text":"- Incidence of Antidrug Antibodies (ADA) to investigational agents – (sacituzumab tirumotecan (sac-TMT, MK-2870) and patritumab deruxtecan (HER3-DXd))","definition_or_measurement_approach":"Incidence of ADA measured via immunogenicity assays for specified investigational agents (sacituzumab tirumotecan and patritumab deruxtecan)."}

Norway

Earliest CTIS Part Ii Submission Date

28-07-2024

Latest Decision Or Authorization Date

13-08-2024

Processing Time Days

16

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

13-08-2024

Processing Time Days

54

Number Of Sites

4

Number Of Participants

10

Germany

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

16-08-2024

Processing Time Days

29

Number Of Sites

4

Number Of Participants

10

France

Earliest CTIS Part Ii Submission Date

15-05-2024

Latest Decision Or Authorization Date

14-08-2024

Processing Time Days

91

Number Of Sites

3

Number Of Participants

4

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International Corp.

Responsibilities

EUB services (call center and medical services)

Name

Bioclinica Inc.

Name

PPD Global Central Labs

Name

PPD Development LP

Name

Almac Clinical Technologies LLC

Name

Icon Clinical Research Limited

Responsibilities

Central Imaging

Name

Frontage Laboratories Inc.

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}