Clinical study with MK-2870 in combination with Pembrolizumab in individuals who have undergone surgical treatment for their triple-negative breast cancer

Summary description of the study

This study is being conducted to test the safety and efficacy of MK-2870 plus Pembrolizumab and how well this combination works compared to Pembrolizumab plus Capecitabine or Pembrolizumab alone. It will also be investigated whether participants receiving MK-2870 plus Pembrolizumab live longer compared to those receiving Pembrolizumab plus Capecitabine or Pembrolizumab alone. Additionally, quality of life will be measured for all three of these groups. MK-2870 is an experimental drug consisting of a monoclonal antibody in combination with a toxin (KL610023). Antibodies are proteins produced by the immune system that help the body fight foreign substances such as bacteria or viruses, but also tumors. Monoclonal antibodies bind to specific targets on cells. MK-2870 binds to a target on certain cancer cells known as trophoblast antigen 2 (TROP2). Through this binding, the toxin (KL610023) can damage these cancer cells. MK-2870 is not yet approved in Switzerland and is being tested in various studies for the treatment of diseases, including endometrial cancer and breast cancer. Pembrolizumab (MK-3475) is an antibody that can prevent the tumor from deceiving the immune system and thus enhance the body's natural fight against the tumor. Capecitabine is an orally administered chemotherapy drug used to treat various types of cancer, including breast cancer, colorectal cancer, and stomach cancer. It is converted in the body into a substance that inhibits the growth of cancer cells. Approximately 1530 patients are expected to participate in the study worldwide. In Switzerland, about 15 patients will participate in this study. The total duration of the study is approximately 5 to 10 years.

(BASEC)

Intervention under investigation

After detailed explanation, thorough eligibility assessment, and collection of medical history, the patient will be enrolled in the study and randomly assigned (1:1 ratio) to one of the two treatment groups. After assignment, patients in group 1 will receive MK-2870 and Pembrolizumab or in group 2 either Pembrolizumab plus Capecitabine or Pembrolizumab alone.

• Group 1: Receives the experimental drug MK-2870 and Pembrolizumab.

• Group 2: Receives either Pembrolizumab plus Capecitabine or Pembrolizumab alone.

For participants in group 2, the study physician will choose which of the two options will be administered. Participants must remain on the selected chemotherapy for the entire treatment duration.

MK-2870 and Pembrolizumab will both be administered via a needle in the arm. This is referred to as intravenous infusion. MK-2870 will be administered once every 2 weeks, Pembrolizumab once every 6 weeks. Capecitabine will be administered orally as prescribed by the study physician.

This study is an open-label study. This means that both the sponsor, the study physician, and the participants know which group they have been assigned to.

As part of the study visits, various measures and examinations will also be performed, such as imaging procedures like CT, MRI, as well as the collection of blood, urine, or tissue samples, and physical examination including checking vital signs (pulse, blood pressure, etc.). This list is not exhaustive and other examinations may also be conducted.

During and after the treatment phase, health status will be regularly monitored for any progression of the cancer disease through imaging examinations (for example, CT and/or MRI scans). In case of disease worsening, patients will visit the study center at least one more time for a safety follow-up visit.

After the last visit to the study center as part of the study, the study physician or study team will contact participants approximately every 12 weeks or at shorter intervals to check their health status.

(BASEC)

Disease under investigation

Breast cancer is the most commonly diagnosed malignant cancer and the leading cause of cancer death among women worldwide. Triple-Negative Breast Cancer (TNBC) accounts for about 10% to 15% of all breast cancer cases. TNBC is associated with a higher tumor grade, younger age at diagnosis, increased risk of recurrence after removal, as well as poorer clinical outcomes. Some individuals with early-stage TNBC do not achieve pathological complete response (pCR) after surgery. The CREATE-X study examined the use of Capecitabine as adjuvant treatment for individuals with early HER2-negative breast cancer who had residual tumors after surgery. HER2 is one of the three receptor types that are absent in TNBC. Capecitabine was compared to standard therapy and showed an advantage in disease-free survival. Overall survival was also longer in the Capecitabine group than in the control group. A previous evaluation of Capecitabine also showed improved disease-free survival and overall survival for TNBC patients when Capecitabine was administered in combination with other systemic treatments. These data establish Capecitabine as a treatment option for adjuvant therapy for patients with early-stage TNBC who do not achieve pCR. The KEYNOTE-522 study demonstrated the benefit of adding Pembrolizumab over a one-year period to neoadjuvant chemotherapy. Patients who do not achieve pCR after neoadjuvant chemotherapy have, compared to other patients with pCR, higher relapse rates and increased mortality. Therefore, there is an unmet medical need for new therapies for patients with TNBC who do not achieve pCR after surgery. This clinical study will investigate MK-2870 plus Pembrolizumab compared to standard chemotherapy, at the discretion of the treating physician (Pembrolizumab alone or in combination with Capecitabine), for the treatment of patients with TNBC who do not achieve pCR at surgery after neoadjuvant therapy with Pembrolizumab plus chemotherapy. The addition of MK-2870 to Pembrolizumab for these patients has the potential to improve the prognosis of this disease. Participants must be in good general health and meet certain laboratory values to be eligible for the study. The laboratory values must reflect adequate organ function (for example, of the blood system, kidneys, and liver).

(BASEC)

Sponsor

MSD Merck Sharp & Dohme AG, Switzerland Merck Sharp & Dohme LLC, USA

(BASEC)

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Zurich

(BASEC)

Date of authorisation

25.06.2024

(BASEC)

Results of the trial