Tumor Treating Fields dually activates the STING and AIM2 pro-inflammatory signaling pathways that drive early anti-tumor immune responses

Novocure (NASDAQ: NVCR) today announced that a new study published in the Journal of Clinical Investigation (JCI) finds treatment with Tumor Treating Fields (TTFields) mediated cell disruption activates the immune system and triggers an anti-tumor cell response that may be effectively used together with existing immunotherapy approaches in the treatment of solid tumors, with limited systemic toxicity.

“TTFields’ ability to activate a downstream immune response, effectively turning a cold tumor hot, is a unique element of TTFields therapy,” said Uri Weinberg, Novocure’s Chief Science Officer. “Given the depth of clinical research focused on the use of immunotherapies and the broad applicability of TTFields, this could be critical to the treatment path for solid tumor cancers.”

Preclinical research has shown evidence that TTFields may induce a pro-inflammatory and broader immunological effect on tumor cells. This study outlines translational research by Dr. Dongjiang Chen and colleagues from the David Tran Laboratory of Quantitative Cancer Research at the University of Florida. Preclinical data demonstrated that treatment with TTFields directly disrupted the nuclear envelope of glioblastoma (GBM) tumor cells. This led to leakage of DNA that activates the cGAS/STING and AIM2 signaling pathways, driving early anti-tumor immune responses. Further, a genetic signature was identified in patients treated with TTFields therapy indicating an acquired immune response. Collectively, these novel preclinical and patient data further elucidate the downstream cellular processes resulting from TTFields’ mechanism of action that support the potential for a therapeutic advantage when used together with immunotherapy, with limited systemic toxicity.

Based on these findings, Dr. David Tran, Chief of the Division of Neuro-Oncology, at the McKnight Brain Institute at the University of Florida, designed the phase 2 pilot 2-THE-TOP clinical study, evaluating the use of TTFields therapy together with the anti-PD-1 therapy (pembrolizumab) and chemotherapy (temozolomide) for the treatment of newly diagnosed GBM in 25 patients. In November 2021, updated data from the ongoing 2-THE-TOP study was presented at the Society for Neuro-Oncology (SNO) 2021 Annual Meeting. These preliminary data showed 19 patients with greater than 9 months of follow-up displayed a median progression-free survival (primary endpoint) of at least 11.2 months. Additionally, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab was administered and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014). This finding is in line with the JCI publication, and contributes to the building body of evidence suggesting TTFields’ mechanism of action induces a downstream signaling pathway that initiates an active immune response that aids the body’s ability to fight cancer cells.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 22,000 patients have been treated with TTFields therapy.

About Novocure

Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of its innovative therapy, Tumor Treating Fields. Novocure’s commercialized products are approved in certain countries for the treatment of adult patients with glioblastoma and in the U.S. for the treatment of adult patients with malignant pleural mesothelioma. Novocure has ongoing or completed clinical trials investigating Tumor Treating Fields in brain metastases, gastric cancer, glioblastoma, liver cancer, non-small cell lung cancer, pancreatic cancer and ovarian cancer.

Headquartered in Jersey, and with a growing global footprint, Novocure has regional operating centers in Root, Switzerland, Portsmouth, New Hampshire and Tokyo, as well as a research center in Haifa, Israel. For additional information about the company, please visit Novocure.com and follow @Novocure on LinkedIn and Twitter.

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