On November 16, 2023 Circio Holding ASA (OSE: CRNA), a biotechnology company developing novel circular RNA and immunotherapy medicines, reported that it has entered into a collaboration with Georgetown University as part of a collaborative research support agreement with Janssen Scientific Affairs, LLC (Janssen) and a drug supply agreement with Bristol Myers Squibb (BMS) to test its drug candidate TG01 in combination with daratumumab (anti-CD38) and nivolumab (anti-PD1) in patients with RAS-mutated pancreatic cancer and patients with non-small cell lung cancer (NSCLC) (Press release, Circio, NOV 16, 2023, View Source [SID1234637733]).
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Mutations in the RAS-family of genes are a major cause of cancer and found in over 90% of pancreatic and 30% of NSCLC cancer patients. RAS-mutated cancers typically have poor prognosis, and few targeted treatment options exist. The only approved RAS-targeting pharmaceuticals are small molecule inhibitors of the specific G12C KRAS mutation, which covers around 40% of RAS-mutated lung cancers, and the medical need for novel treatment alternatives for mutant RAS cancer remains high. Furthermore, anti-PD1 resistance is emerging as a major problem in immunotherapy, and more than 80% of patients with advanced tumors still do not respond to such treatment.
To further study this unmet medical need, Georgetown University is pursuing a phase 2 study to test the combination of daratumumab provided by Janssen, nivolumab provided by BMS, and TG01 provided by Circio in immunotherapy-naïve pancreatic cancer and in anti-PD1 resistant NSCLC. The scientific hypothesis behind the study is based on ground-breaking research led and published by Prof. Samir Khleif and colleagues, demonstrating that elimination of dysfunctional CD8 T-cells by anti-CD38, followed by priming of new effector T-cells by a cancer vaccine, reinstated and strengthened efficacy of PD1 checkpoint blockade in pre-clinical models.
Prof. Samir Khleif, Georgetown University, said: "Resistance to checkpoint blockade remains one of the most challenging problems in treating cancer patients and represents a significant unmet medical need. We are very pleased to have established this collaboration to test a novel immunotherapy combination regimen with the intention of overcoming immunotherapy resistance. The combination of anti-CD38, anti-PD1 and a cancer vaccine has demonstrated highly potent in preclinical in vivo models, and we are eager to evaluate how these findings will translate in the clinic."
The trial will be led by Georgetown University in Washington D.C, USA. The triple therapy combination will be tested in 54 patients in total, 27 immunotherapy-naïve KRAS-mutated patients with pancreatic cancer and 27 KRAS-mutated patients with NSCLC who have progressed on prior anti-PD1 therapy.
Dr. Erik Digman Wiklund, Chief Executive Officer of Circio Holding ASA, added: "We continue to see increasing interest in our mutant KRAS program, and the Georgetown phase 2 study will be the third investigator-sponsored clinical trial with the enhanced TG01 vaccine. This will be the first time TG01 is tested in lung and non-resectable pancreatic cancer, potentially opening up new indications for future development. Collaborations such as this is at the core of the TG01 development strategy, and shows that we are continuing to execute on our strategy of advancing our KRAS program through external development in multiple settings and geographies."
Circio has been awarded two prestigious research grants from Innovation Norway (IN) and the Norwegian Research Council (NRC) to advance the TG program in several clinical studies. This phase 2 trial at Georgetown will be the first study where TG01 is combined with anti-CD38 and anti-PD1, and the first time the vaccine is tested in NSCLC. Circio will be responsible for TG01 drug supply and scientific support towards specific KRAS-related immunological assays, supported through the IN and NRC research grants. Janssen will contribute with funding for the study and daratumumab supply, and BMS will provide supply of nivolumab. The study protocol has been approved by the US FDA, and it is anticipated that the first patient will be enrolled at Georgetown before the end of 2023.