Substudy 06C: A Study of Sacituzumab Tirumotecan (MK-2870) With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)

Launched by MERCK SHARP & DOHME LLC · Jun 17, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring how safe and effective a combination of three treatments—sacituzumab tirumotecan, pembrolizumab, and a type of chemotherapy—can be for patients with certain types of esophageal cancer that cannot be surgically removed or has spread to other parts of the body. The goal is to find out if this treatment can help patients who are starting their first round of treatment for this serious condition. The study will first assess the safety of these treatments together before moving on to see how well they work.

To participate in the trial, patients should have a confirmed diagnosis of locally advanced or metastatic gastroesophageal adenocarcinoma, meaning their cancer has spread and can't be removed with surgery. They should not have received prior treatments for this cancer and must meet certain health criteria, such as having good organ function. Participants will receive the study treatments and will be closely monitored for their safety and response to the therapy. This trial is currently recruiting patients, and it offers an opportunity for individuals facing this challenging diagnosis to contribute to important medical research while potentially gaining access to new treatment options.

Gender

ALL

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 1L gastroesophageal adenocarcinoma
• • Has gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu-positive are excluded. HER2 status is not required if HER2/neu testing is not mandatory per local standard of care (SOC)
• • Is not expected to require tumor resection during the treatment course
• • Has not had prior systemic therapy administered in the recurrent or metastatic setting
• • Has provided an archival tumor tissue sample or most recently obtained core, or incisional, or excisional biopsy for a tumor lesion
• • 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 blind independent review committee (BICR)
• • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 3 days before allocation/randomization.
• • Has a life expectancy of at least 6 months
• • 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 randomization.
• • Who has 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 (ART)
• 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/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
• • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• • Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC)
• • Has received prior treatment with a topoisomerase I inhibitor-based ADC and/or a topoisomerase I inhibitor-based chemotherapy
• • Has received prior systemic anticancer therapy including investigational agents 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, 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/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• • 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
• • Has 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
• • Have not adequately recovered from major surgery or have ongoing surgical complications