Trovagene, Inc., a developer of cell-free molecular diagnostics, has begun a study to determine utility of its Precision Cancer Monitoring (PCM) technology for predicting response to treatment in advanced melanoma patients receiving one or a combination of the novel immunotherapy agents Yervoy (ipilumumab), a CTLA-4 inhibitor, and Opdivo (nivolumab), a PD-1 inhibitor.

The 50-patient study will be led by researchers at Memorial Sloan Kettering Cancer Center (MSK). BRAF and NRAS oncogene mutations will be used as biomarkers to monitor tumour dynamics in treated patients. Primary objectives of the study include determining 1) if circulating tumour (ctDNA) can determine response to therapy early, and 2) if ctDNA results correlate with the clinical course of disease.

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The need to quantitatively monitor early response to cancer immunotherapy is widely recognised given the lack of response biomarkers, toxicities with combination immunotherapy, and the challenge of pseudo-progression, which is characterised by initial tumour swelling that is observed with traditional imaging tools.

"As more immunotherapies become available for the treatment of cancer, it becomes more important to have non-radiographic tools to assess treatment effects," stated Paul Chapman, M.D., a medical oncologist at MSK who will oversee the study.

"Responses to immunotherapy vary greatly in timing and extent, and radiographic responses may not reflect accurately the true response. A rapid, accurate, and quantitative method to determine therapeutic effect as early as possible could help align new treatment strategies to patients' needs."

"In this study, we attempt to better inform clinicians of the early benefits of immunotherapy in advanced melanoma," said Mark Erlander, PhD, chief scientific officer of Trovagene.

"We have previously shown in lung, colorectal, and pancreatic cancers that our PCM platform can detect response to therapy within days of treatment. Here, we intend to demonstrate that quantitative monitoring of driver mutations can provide reliable insight into tumour dynamics and response to immunotherapy, which is particularly important given the shortfalls of cancer imaging in this clinical situation."

Cancer immunotherapy uses the body's own immune system to fight cancer. Immunotherapy works by either stimulating a patient's immune system to attack cancer cells or supplementing the immune system with what it needs, such as antibodies, to fight cancer. New immunotherapy treatments such as anti-PD-1 antibodies Opdivo (nivolumab) and Keytruda (pembrolizumab), have demonstrated higher rates of response in certain difficult-to-treat cancer types, however, these treatments can present unique challenges beyond those seen with traditional chemotherapy or targeted oncology agents. One such challenge is the concept of pseudo-progression, which is tumour enlargement observed when traditional imaging modalities are used to determine response to immunotherapy treatment.

Pseudo-progression is thought to be caused by T-cell infiltration and inflammation of the tumor as it responds to immunotherapy. However, this tumor enlargement may be beneficial and may precede a prolonged response to the immunotherapy. As a result, cancer imaging is not always a reliable method to determine response to immunotherapy, and clinicians are increasingly relying on biopsies to confirm therapeutic efficacy of these treatment regimens. In these clinical situations, the use of a non-invasive liquid biopsy has potential provide an important solution for determining and monitoring treatment response to novel immuno-oncology agents, such as the PD-1 inhibitors.

Yervoy and Opdivo are registered trademarks of Bristol-Meyers Squibb Company. Keytruda is a registered trademark of Merck & Co., Inc.