Phase 3 Multicenter Randomized Study Comparing Efficacy and Safety of Sacituzumab Tirumotecan Versus Physician's Choice in Advanced Gastroesophageal Adenocarcinoma
- Trial ID
- 2023-505423-31-00
- Protocol
- MK-2870-015
- Sponsor
- Merck Sharp & Dohme LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, multicenter, open-label, randomized study is to compare the efficacy of **MK-2870** versus treatment of physician's choice (TPC) in terms of overall survival (OS) in patients with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma. This comparison is clinically relevant as it aims to determine the potential of MK-2870 to improve survival outcomes in this patient population, which is critical given the limited treatment options and poor prognosis associated with these advanced cancers.
Secondary objectives include:
- Comparing MK-2870 to TPC with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR).
- Comparing MK-2870 to TPC with respect to objective response rate (ORR) per RECIST 1.1 as assessed by BICR.
- Evaluating the duration of response (DOR) per RECIST 1.1 as assessed by BICR in participants who demonstrate confirmed complete response (CR) or partial response (PR) during or after treatment with MK-2870 and TPC.
- Evaluating the safety and tolerability of MK-2870.
Participants
The clinical trial involves a total of **369 participants** diagnosed with **advanced or metastatic gastric adenocarcinoma**, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on specific inclusion criteria, such as having a histologically- or cytologically-confirmed diagnosis of the specified conditions, and having progressed on at least two prior chemotherapy and/or immunotherapy regimens. The trial does not include a vulnerable population. Participants are required to have adequate organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Lifestyle considerations such as diet and physical activity are not specified, but participants must have the ability to swallow oral medication if applicable. The trial population was carefully selected to ensure the inclusion of individuals with measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and those with adverse events from previous therapies must have recovered to a certain extent. The study does not focus on any specific lifestyle habits beyond the medical and functional criteria outlined.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase III study to evaluate the efficacy and safety of MK-2870 compared to the treatment of physician's choice in patients with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma. The trial aims to assess the primary endpoint of overall survival (OS) and secondary endpoints including progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and the number of participants experiencing adverse events (AEs) or discontinuing the study intervention due to AEs. The trial is expected to commence recruitment on May 1, 2024, and conclude by May 5, 2028, with a maximum treatment period of 48 weeks for participants.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically- or cytologically-confirmed diagnosis, previous treatment history, and adequate organ function. Following randomization, participants will receive either MK-2870 or the treatment of physician's choice, with regular follow-up visits to monitor treatment response and safety. These visits will include assessments of disease progression, adverse events, and overall health status. The end-of-study visit will occur after the completion of the treatment period or upon early termination, which may occur due to disease progression, unacceptable toxicity, or withdrawal of consent.
The expected length of participant involvement is up to 48 weeks, with conditions for early termination including significant adverse events, disease progression, or participant withdrawal. The trial will utilize intravenous infusion for the administration of MK-2870, with other treatments administered as per standard care practices. The study will ensure rigorous monitoring and data collection to evaluate the comparative effectiveness of MK-2870 in the specified patient population.
Treatment
The clinical trial involves the administration of several **experimental medications** and comparator treatments. **MK-2870**, also known as sacituzumab tirumotecan, is the primary investigational drug. It is a **biological** agent formulated as a **powder for solution for injection**. The active substance is a humanized IgG1 monoclonal antibody against TROP2, conjugated to KL610023. The drug is administered via **intravenous infusion** at a maximum daily dose of 4 mg/kg, with a total maximum dose of 416 mg/kg over a treatment period of 48 weeks.
**Irinotecan hydrochloride** is used as a comparator treatment. It is a **chemical** compound administered as an **intravenous infusion**. The pharmaceutical form is denoted as PHF00230MIG. The maximum daily dose is 150 mg/m², with a total maximum dose of 14,400 mg/m² over the same treatment period.
**Paclitaxel** is another comparator treatment, also a **chemical** compound, administered via **intravenous infusion**. It shares the same pharmaceutical form as irinotecan, PHF00230MIG. The maximum daily dose is 80 mg/m², with a total maximum dose of 11,520 mg/m² over 48 weeks.
**Docetaxel** is included as a comparator, administered as an **intravenous infusion**. It is a **chemical** compound with a pharmaceutical form of PHF00230MIG. The maximum daily dose is 75 mg/m², with a total maximum dose of 4,800 mg/m² over the treatment period.
**Trifluridine and tipiracil** are administered as a combination therapy, taken orally. This **chemical** treatment is provided in the pharmaceutical form PHF00082MIG. The maximum daily dose is 70 mg/m², with a total maximum dose of 33,600 mg/m² over 48 weeks.
**Paracetamol**, combined with buclizine hydrochloride and codeine phosphate, is used as an auxiliary treatment. This **chemical** combination is administered through other unspecified routes, with no specified maximum daily or total dose.
**H2-Receptor Antagonists** and **glucocorticoids** are also included as auxiliary treatments. Both are **chemical** compounds administered through other unspecified routes, with no specified maximum daily or total dose.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to compare the efficacy and safety of MK-2870 against the treatment of physician's choice in patients with advanced or metastatic gastroesophageal adenocarcinoma.
Efficacy
The efficacy of the clinical trial will be assessed using several key endpoints. The primary endpoint is **Overall Survival (OS)**, which will measure the length of time from randomization until death from any cause. Secondary endpoints include **Progression-free Survival (PFS)**, which evaluates the time from randomization to disease progression or death, **Objective Response Rate (ORR)**, which assesses the proportion of participants with a significant reduction in tumor size, and **Duration of Response (DOR)**, which measures the time from the first occurrence of a documented response to disease progression. Additionally, the trial will monitor the number of participants who experience an adverse event (AE) and those who discontinue the study intervention due to an AE.
The trial is designed to compare the efficacy and safety of MK-2870 versus the treatment of the physician's choice in patients with advanced or metastatic gastroesophageal adenocarcinoma. Efficacy assessments will be conducted at specified intervals throughout the study, with data collection and analysis performed according to standardized protocols. The trial will utilize validated scales and criteria, such as the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, to ensure consistent and reliable measurement of efficacy parameters. The study is expected to conclude by May 2028, with recruitment starting in May 2024.
Inclusion and Exclusion Criteria
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 adequate organ function.
- 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 measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.
- 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 for at least 4 weeks, 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 a 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. Administration of killed vaccines are allowed.
- Is currently receiving a strong 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 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 severe hypersensitivity (Grades ≥3) to the study interventions, any of their excipients, and/or to another biologic therapy.
- Has a history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 May 2024 | 15 |
 Denmark | Not Recruiting | 01 May 2024 | 9 |
 France | Not Recruiting | 01 May 2024 | 25 |
 Germany | Not Recruiting | 01 May 2024 | 21 |
 Italy | Not Recruiting | 01 May 2024 | 31 |
 Poland | Not Recruiting | 01 May 2024 | 10 |
 Spain | Not Recruiting | 01 May 2024 | 25 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
- | Other | PHF00231MIG | OTHER USE | 00 | 48 | H02AB |
MK-2870 | Test | SOLUTION FOR INJECTION | INTRAVENOUS INFUSION | 4 | 48 | PRD11447874 |
TRIFLURIDINE, COMBINATIONS | Comparator | PHF00082MIG | ORAL USE | 70 | 48 | SCP12480833 |
IRINOTECAN | Comparator | PHF00230MIG | INTRAVENOUS INFUSION | 150 | 48 | SCP160940 |
PACLITAXEL | Comparator | PHF00230MIG | INTRAVENOUS INFUSION | 80 | 48 | SCP129816 |
DOCETAXEL | Comparator | PHF00230MIG | INTRAVENOUS INFUSION | 75 | 48 | SCP126226 |
- | Other | PHF00245MIG | OTHER USE | 00 | 48 | R06A |
PARACETAMOL | Other | PHF00082MIG | OTHER USE | 00 | 48 | SCP1081917 |
- | Other | - | OTHER USE | 00 | 48 | A02BA |