Clinical Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan (MK-5909) in People with Gastrointestinal Cancer

Zusammenfassung der Studie

This study investigates how effective and safe the drug Raludotatug Deruxtecan (R-DXd) is in treating various cancers in the gastrointestinal tract in patients who have already received prior therapies. The following data will be evaluated: • how many treated participants show a complete or partial tumor regression, also known as objective response rate • the duration of response and the probability of overall survival the duration of progression-free survival, which corresponds to the period during which patients show no deterioration of their disease. • the safety of the study drug • investigation of biomarkers, which are specific medical characteristics that can help show how well patients respond to treatment, what side effects it shows, and how it reacts in the body. Approximately 160 people worldwide are expected to participate in this study, including about 12 people in Switzerland. The total study duration is approximately 4.5 years.

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Untersuchte Intervention

The study is a Phase 2 study that is open-label, meaning that both the participants and the study physician and sponsor know which treatment the patients are receiving. Each participant is expected to participate in the study for 3 years, starting with the signing of the informed consent form.

After thorough education, a detailed eligibility assessment of about 28 days, and collection of medical history, the patient will be enrolled in the study. Based on the disease, patients will be assigned to one of four treatment groups:

• Group 1: Patients with advanced pancreatic cancer who have received prior therapy (approximately 40 participants)

• Group 2: Patients with advanced bile duct cancer who have received at least one prior therapy (approximately 40 participants)

• Group 3: Patients with advanced colorectal cancer who have received prior therapy (approximately 40 participants)

• Group 4: Patients with advanced stomach or esophageal cancer who have received prior therapy (approximately 40 participants)

Treatment occurs every 3 weeks over a period of one year. Since this is a non-randomized study, each participant will receive R-DXd at a dosage of 5.6 mg/kg every 3 weeks via a needle in the arm. This is referred to as intravenous infusion. After the treatment ends, participants will continue to be monitored for another 2 years.

During study visits, various measures and examinations may occur, such as imaging studies (CT scans, MRIs), blood and urine tests, tumor biopsy collection, assessment of general health status, and discussions with medical personnel. The study team may also contact participants between visits and after the completion of the study drug to inquire about their health status.

Investigated study drug:

R-DXd is a special type of cancer treatment known as an antibody-drug conjugate. It consists of a monoclonal antibody to which a chemotherapy agent is attached. A monoclonal antibody is a molecule that targets specific cancer cells, but it can also bind to healthy cells in the human body. Chemotherapy is a type of cancer treatment that kills rapidly growing and dividing cells. Typically, these are cancer cells, but healthy cells can also be affected.

R-DXd is a novel medication that specifically targets a protein called cadherin-6 (CDH6). CDH6 plays an important role in cell adhesion, organ development, and the transition of epithelial cells to mesenchymal cells, a process where cells change their properties to move better and fulfill different functions. CDH6 is overexpressed in several types of cancer and plays a role in spreading to other organs. Higher levels of CDH6 protein are associated with a poorer prognosis in cancer patients. R-DXd works by binding to CDH6 on the tumor cell, entering the cell, and releasing the chemotherapy. The chemotherapy component of R-DXd may also affect surrounding cancer cells that may not express the CDH6 protein. In a Phase 1 study, R-DXd showed promising effects against tumors, with tumor shrinkage observed in all six participants.

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Untersuchte Krankheit(en)

The study includes people with various types of cancer in the gastrointestinal tract, including pancreatic cancer, bile duct cancer, colorectal cancer, as well as cancer of the stomach and esophagus. • Globally, pancreatic cancer is the seventh most common cause of cancer-related deaths. In 2022, there were about 510,992 newly diagnosed cases of pancreatic cancer and around 467,409 deaths. The 5-year survival rate for metastatic pancreatic cancer is only 3%. • Biliary tumors include cancers of the bile ducts, known as cholangiocarcinomas, as well as cancers of the gallbladder. In the USA, about 12,400 new cases and 4,500 deaths from biliary tumors were projected for 2024, with a 5-year survival rate for metastatic biliary tumors of only 2% to 3%. • Colon and rectal cancer, known as colorectal cancer, is the third most common cancer diagnosis worldwide, with approximately 1.9 million new cases in 2022 and about 904,000 deaths annually. The 5-year survival rate for metastatic colorectal cancer is only 14%. • Cancer in the esophagus and stomach, known as gastroesophageal adenocarcinomas, is the fifth most common cancer worldwide and the fourth leading cause of cancer-related deaths, with about 968,800 new cases and 660,200 deaths in 2022. The 5-year survival rate for metastatic gastroesophageal adenocarcinomas is only 7%. These cancers were selected because they not only have a poor prognosis but also an unmet medical need for alternative therapeutic options.

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Sponsor

MSD Merck Sharp & Dohme AG, Lucerne

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Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Zürich

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Datum der Bewilligung durch die Ethikkommission

17.06.2025

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Ergebnisse der Studie