Gastroesophageal Cancer
Conditions
Keywords
Gastroesophageal cancer, Gastroesophageal adenocarcinoma, Gastric adenocarcinoma, Esophageal adenocarcinoma
Brief summary
This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with advanced/metastatic gastroesophageal adenocarcinoma. The primary hypothesis of this study is sacituzumab tirumotecan is superior to TPC with respect to Overall Survival (OS).
Interventions
BIOLOGICALSacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan as 4mg/kg IV infusion on days 1, 15, and 29 of every 42-day cycle.
Trifluridine-tipiracil will be administered at 35 mg/m\^2 as tablet orally twice a day on days 1-5 and 8-12 of every 28-day cycle.
DRUGIrinotecan
Irinotecan will be administered at a dose of 150 mg/m\^2 by IV infusion on days 1 and 15 of every 28-day cycle.
DRUGPaclitaxel
Paclitaxel will be administered at a dose of 80 mg/m\^2 by IV infusion on days 1, 8 and 15 of every 28-day cycle.
DRUGDocetaxel
Docetaxel will be administered at a dose of 75 mg/m\^2 by IV infusion on day 1 of a 21-day cycle.
Participants are required to receive prophylactic mouthwash (steroid mouthwash \[dexamethasone or equivalent\] is highly recommended) to mitigate the onset and severity of stomatitis or oral mucositis. Additionally, participants may receive mucoadhesive hydrogel and oral nystatin suspension or other topical antifungal agents. Additional recommended rescue medications are histamine-1 (H1) receptor antagonist, H2 receptor antagonist, acetaminophen or equivalent, and dexamethasone or equivalent, at the investigator's discretion.
Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Supportive care measures may include but are not limited to antidiarrheal agents, antiemetic agents, opiate and non-opiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a histologically or cytologically confirmed diagnosis of advanced, unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma * Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions * Has received, and progressed on, at least 2 prior chemotherapy and/or immunotherapy regimens for advanced, unresectable or metastatic gastroesophageal adenocarcinoma * Participants are eligible regardless of human epidermal growth factor receptor-2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab where available/appropriate * Has provided tumor tissue sample for determination of trophoblast cell-surface antigen 2 (TROP2) status by the central laboratory before randomization for stratification * Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible * Has adequate organ function * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days before randomization * Has ability to swallow oral medication for those who may receive trifluridine-tipiracil * Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART) * Hepatitis B surface antigen (HBsAg)-positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load * Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion criteria
* 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 (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea) * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval (QTcF) to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention * Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before the first dose of study intervention * Has received prior treatment with TROP2-targeted antibody-drug conjugate (ADC), a topoisomerase 1 inhibitor-based ADC, and/or a topoisomerase 1 inhibitor-based chemotherapy * Has received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention * Has received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Is currently receiving a strong and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks * Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention * Has a 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 an active infection requiring systemic therapy * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castlemans's Disease * Has concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid \[DNA\]) and HCV (defined as anti-HCV antibody \[Ab\] positive and detectable HCV ribonucleic acid \[RNA\]) infection * Has severe hypersensitivity (Grades \>=3) to the study interventions, any of their excipients, and/or to another biologic therapy * Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary * Has a history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to ~ 31 months | OS is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to ~ 25 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥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 ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented. |
| Objective Response Rate (ORR) | Up to ~ 25 months | ORR is defined as the percentage of participants with CR (disappearance of all target lesions) or 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. |
| Duration of Response (DOR) | Up to ~ 25 months | For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. 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. DOR as assessed by BICR will be presented. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to ~ 36 months | 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. |
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to ~ 36 months | 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. |
Countries
Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, France, Germany, Hong Kong, Israel, Italy, Japan, Malaysia, Mexico, Peru, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed