On June 16, 2025 Circio Holding ASA (OSE: CRNA), a biotechnology company developing circular RNA technology for gene and cell therapy and mutant RAS-targeting cancer vaccines, reported that interim data from the TG01 phase 1/2 clinical trial in multiple myeloma at Oslo University Hospital (OUS) has been presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 annual meeting in Milan, Italy (Press release, Circio, JUN 16, 2025, View Source [SID1234653913]).
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The results show preliminary signals of clinical efficacy for TG01 vaccination and confirm an excellent safety profile, thus providing justification for continued clinical development for a major unmet medical need. The trial is a collaboration between OUS and Circio to test TG01/QS-21 vaccination as a monotherapy in 20 KRAS or NRAS mutated multiple myeloma patients with remaining measurable disease after completion of standard of care treatment. The aim is to assess whether T-cell responses to mutant RAS induced by TG01 can enhance and prolong the clinical benefit. OUS is the study sponsor, with Dr. Hanne Norseth as the primary investigator.
"RAS-mutant multiple myeloma has poor prognosis and there are currently no available targeted treatment options for this patient population," said Dr. Fredrik Schjesvold, Founder and Leader Oslo Myeloma Center, at Oslo University Hospital, and President of the Nordic Myeloma Study Group "Interim data from the first twelve patients demonstrate the capability of TG01 to induce RAS-specific T-cell responses in a subset of patients, and suggest that these responses are associated with disease stabilization. This is an important early indication of clinical benefit. We look forward to completing the study, including a broad set of genetic and immunological analyses, which will help us build the understanding of how TG01 vaccination can fit as a future treatment option to deepen and prolong responses in this underserved patient population."
Oncogenic RAS mutations drive up to 30% of all cancers and an estimated 15-20% of multiple myelomas, and remain a major unmet medical need with few effective treatment alternatives. Circio has previously been awarded two prestigious research grants from Innovation Norway and the Norwegian Research Council to advance the TG mutant RAS cancer vaccine program. These grants have provided funding towards two active clinical studies, including the present multiple myeloma study at OUS, Norway, and a phase 2 trial at Georgetown University, Washington D.C. USA, where TG01 is tested in pancreatic and lung cancer.
"Consistent with our prior observations in pancreatic cancer, it is very reassuring that this early-stage multiple myeloma trial has generated results showing immunological activity of the TG01 vaccine associated with clinical benefit," said Dr. Victor Levitsky, Chief Scientific Officer of Circio Holding ASA. "The biomarker findings are consistent with the current understanding of tumor immune control requiring a proper match between the characteristics of the tumor and the of patient´s genetic buildup. This important connection provides a mechanistic validation of clinical benefit and suggests specific biomarkers to select patients who can benefit most from TG01 treatment in follow-up clinical studies. We will continue to pursue our strategy to develop TG01 through external partnerships in parallel with our core in house circular RNA program."
Poster title:
The phase I/II TG01-study: Vaccinating against RAS-mutated Multiple Myeloma
Presentation date and location:
14 June 2025, EHA (Free EHA Whitepaper) 2025 Annual Meeting, Milan – Italy
The main conclusions from the poster presentation were as follows:
Available data demonstrate excellent tolerability and safety of TG01/QS-21 vaccination
50% (6/12) of vaccinated patients show vaccine-induced specific T-cell responses against mutant K/N-RAS-peptides
50% (6/12) of patients remain on study with stable disease (SD), no objective responses have so far been observed
67% (4/6) of patients with SD had a K/N-RAS-peptide specific immune response by ELISPOT (1/2 negative patients fell very narrowly below positivity threshold)
Enrollment and analysis of the TG01 vaccine-specific responses are ongoing