Substudy 06C: A Study of Investigational Agents With Pemb... | NCT06469944

NCT06469944

ID	Type	Description
MK-3475-06C	Other Identifier	MSD
KEYMAKER-06C	Other Identifier	MSD
2023-509307-33-00	Registry Identifier	EU CT
U1111-1299-8084	Registry Identifier	UTN

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab plus Chemotherapy	Active Comparator	Participants will receive pembrolizumab 400 mg via intravenous (IV) injection on day 1 of every 6 week cycle (Q6W) for up to 18 cycles (up to ~2 years) AND investigator's choice of CAPOX chemotherapy (capecitabine 1000 mg/m^2 orally twice daily for 14 days every 3 weeks (Q3W) and oxaliplatin 130 mg/m^2 via IV infusion Q3W) OR mFOLFOX6 chemotherapy (oxaliplatin 85 mg/m^2 via IV infusion Q3W; 5-Fluorouracil (5-FU) 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once every 2 weeks (Q2W); and leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W).	Biological: Pembrolizumab Drug: Capecitabine Drug: Leucovorin Drug: Levoleucovorin Drug: 5-Fluorouracil (5-FU) Drug: Oxaliplatin
Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy	Experimental	Participants will receive sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to ~2 years) AND investigator's choice of capecitabine 1000 mg/m^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once Q2W AND leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W.	Biological: Pembrolizumab Biological: Sacituzumab Tirumotecan (sac-TMT) Drug: Capecitabine Drug: Leucovorin Drug: Levoleucovorin Drug: 5-Fluorouracil (5-FU)
Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy	Experimental	Participants will receive patritumab deruxtecan via IV infusion on Days 1 and 22 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to ~2 years) AND investigator's choice of capecitabine 1000 mg/m^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once Q2W AND leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Administered via intravenous (IV) infusion.	Pembrolizumab plus Chemotherapy Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)	DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be reported.	Up to approximately 28 days
Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 28 days
Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 28 days
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.

Secondary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line (1L) gastroesophageal adenocarcinoma
Is not expected to require tumor resection during the treatment course
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
Core/excisional biopsy of a tumor lesion not previously irradiated has been provided
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
Has adequate organ function
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 blinded independent central review (BICR)
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the first dose of study intervention
Has a life expectancy of at least 6 months
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
Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

Has squamous cell or undifferentiated gastroesophageal cancer.
Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma
Has experienced weight loss >20% over 3 months before the first dose of study intervention
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
Has Grade ≥2 peripheral neuropathy
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
Has history of human immunodeficiency virus (HIV) infection with Kaposi's sarcoma and/or Multicentric Castleman's Disease
Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor receptor 3 (HER3) targeted agents
Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC) and/or a topoisomerase I inhibitor-based chemotherapy
Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
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)
Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
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
Has known additional malignancy that is progressing or has required active treatment within the past 3 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
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
Has active autoimmune disease that has required systemic treatment in the past 2 years
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
Has an active infection requiring systemic therapy
Has concurrent active hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable HBV DNA) and hepatitis C virus (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
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
Has gastrointestinal (GI) obstruction, poor oral intake, or difficulty in taking oral medication
Has poorly controlled diarrhea
Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention
Has history of allogeneic tissue/solid organ transplant
Has not adequately recovered from major surgery or has ongoing surgical complications

Label	URL
Merck Clinical Trials Information	View source
Plain Language Summary	View source

ID	Term
D004938	Esophageal Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D004066	Digestive System Diseases
D004935	Esophageal Diseases
D005767	Gastrointestinal Diseases

ID	Term
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D056831	Coordination Complexes
D009930	Organic Chemicals

ID	Term
C582435	pembrolizumab
D000069287	Capecitabine
D002955	Leucovorin
D058766	Levoleucovorin
D005472	Fluorouracil
D000077150	Oxaliplatin
C000710748	patritumab deruxtecan