INTeRCePT: Clinical Study to Begin

Blood cancers are usually well treatable with a combination of chemotherapy, targeted drugs, and immunotherapy. However, cancer recurs in many patients after some time. In Switzerland alone, over 1100 people die annually from leukemia and lymphoma. In particular, aggressive lymphomas or acute lymphoblastic leukemia are difficult to treat.

In INTeRCePT we aim to determine which therapies are most effective for both children and adults with blood cancer. Our goal is to increase the response rate of patients to therapy by 50%.

The Journey So Far

The first three years of INTeRCePT have been dedicated to research and discovery. Our team collected and analyzed tissue and blood samples in the lab, testing various medications and their effects on cells at a single-cell level. We closely examined tumors over time, watching how they responded to drug treatments by looking at individual cells. This detailed study measured the expression (amount) of all genes, and specific proteins to understand how the cells behaved individually and in communication with each other. We also studied how the cells isolated from patients responded to drugs, again at the level of individual cells. Another important part of our research is to understand how certain key cells drive tumor growth and how these tumor cells interact with the immune system. We were able to generate an extensive dataset that will be crucial for the next phase of our study.

What’s Next?

Starting early next year, we will launch a follow-up trial on high-risk patients. This trial will include 50 participants: 25 will receive standard therapy, while the other 25 will undergo a tailored panel of cellular analyses to improve outcome prediction in aggressive B cell lymphoma. This approach includes CAR-T cell therapy and additional treatments, with the goal of determining the most effective combination of medications and treatments for each patient. Our aim is to identify which patients have a high risk of relapse (and likely need additional treatment) and which do not, allowing us to provide more personalized and effective care. We aim to complete this trial by the end of 2026, with an option open it in other centers (e.g. Basel and Bellinzona).

At the same time, we will organize and finance a trial that will focus on treatments customized to how individual cells respond to drugs and to the specific treatment plans of patients. We will also expand our data science team to integrate multiple types of biological data, which we hope will lead to new discoveries.

Goals and Expectations

The primary goal of INTeRCePT is to improve the response rate to treatment in patients with B-cell and Mantle cell lymphoma (MCL). Currently, the standard-of-care treatment is CART-T cells which has a response rate of 40%. We aim to increase this to 60%, corresponding to a 50% improvement. To achieve this, we will conduct detailed analyses and create a comprehensive map of drug responses at the single-cell level. This information will help us develop a more widely applicable method for treating blood cancer in the future.

Scientific Advisory Board Insights

We are thankful for the continuing support of the Scientific Advisory Board (SAB), which has expressed strong support for the progress made so far and is pleased with the scientific advancements and the interdisciplinary collaboration that has benefited many young scientists. The SAB acknowledges the challenges in achieving a 60% response rate within the current project timeframe. Therefore, they recommend continuing with a diagnostic trial to validate our assay and then proceeding with an efficacy trial after the current project ends.

Even if the primary objective of enhancing the response rate were not to be fully achieved within the current project, the validation of the INTeRCePT assay itself is a significant milestone. It will set the stage for future studies and improvements in blood cancer treatment strategies.

Looking Forward

The concept of precision medicine from INTeRCePT can serve as a template for planning therapies for a variety of cancer types. The detailed analysis of the dynamic changes in tumor cells and their molecular response to treatment allows conclusions that can be implemented into an optimized treatment plan, thereby improving the prospects for cancer patients. With INTeRCePT, we hope to position the medical research community in Zurich internationally at the forefront in the field of precision oncology of hematological cancers.

We are optimistic about the future of INTeRCePT and the potential breakthroughs it holds. With the start of the clinical trial, we are one step closer to advancing the treatment of blood cancer and improving the lives of many patients.

Prof. Dr. med. Thorsten Zenz
Department of Medical Oncology and Hematology, University Hospital Zurich