Study on a New Combination Therapy for HER2-Positive Bile Duct or Gallbladder Cancer

Bile duct and gallbladder cancers are rare cancers that are usually detected at a late stage. In advanced stages, a cure is generally no longer possible, which is why treatment aims to slow the progression of the disease and alleviate tumor-related symptoms. The current standard of care consists of a combination of the chemotherapy drugs gemcitabine and cisplatin with the antibody durvalumab. This so-called immunochemotherapy is intended to improve quality of life and prolong life expectancy. The TRAP-BTC study is now investigating an alternative combination in which the antibodies pembrolizumab and trastuzumab are used in place of durvalumab, in conjunction with standard chemotherapy. Pembrolizumab is a so-called immune checkpoint inhibitor. It strengthens the body’s own immune system by releasing a “brake” on the immune system (the PD-1 signaling pathway). This allows immune cells to once again actively attack cancer cells. Trastuzumab is a targeted drug that acts against the HER2 surface protein, which is present in elevated levels in some tumors. Blocking this signal inhibits the growth of cancer cells and can also stimulate the immune system to destroy the tumor cells. Both drugs are already approved for the treatment of other types of cancer, such as breast or stomach cancer, but not yet for bile duct cancer.

The goal of this Phase 2 study is to investigate whether the combination of these two antibodies with standard chemotherapy can control the disease more effectively than the current treatment. It is being conducted at approximately six centers in Germany and includes a total of 24 study participants.

Following a screening phase, a treatment phase lasting approximately 24 months will begin, consisting of up to 35 treatment cycles, each lasting three weeks. This is followed by a follow-up period during which patients are examined or contacted every three months. During the treatment phase, regular blood tests, physical examinations, and imaging procedures (computed tomography or magnetic resonance imaging) are performed to monitor the course of the disease.

Women and men aged 18 and older with confirmed HER2-positive bile duct or gallbladder cancer who have not yet received systemic treatment are eligible to participate in this study. Patients must not have any serious comorbidities, particularly severe heart or autoimmune diseases. Pregnancy and breastfeeding also exclude participation. In addition, there is a voluntary accompanying research program. In this program, tumor and blood samples are analyzed for research purposes to better understand how the medications work and which biological characteristics influence the success of treatment. These analyses are intended solely for research and have no impact on individual treatment.