Circio Holding ASA announced interim results from a phase 1/2 clinical trial of TG01, a mutant RAS-targeting cancer vaccine, showing preliminary signals of clinical efficacy in multiple myeloma patients at the European Hematology Association 2025 annual meeting in Milan, Italy.
The trial, conducted at Oslo University Hospital in collaboration with Circio, enrolled 12 of 20 planned patients with KRAS or NRAS mutated multiple myeloma who had remaining measurable disease after completing standard of care treatment. TG01 vaccination combined with QS-21 adjuvant demonstrated an excellent safety profile while inducing specific immune responses in half of the treated patients.
Clinical Activity and Immune Response
TG01 vaccination led to an increase in mutant RAS T-cells in 6 of 12 patients (50%), with 5 of these patients remaining on study with stable disease. Among the 6 patients who achieved stable disease, 67% (4/6) showed K/N-RAS-peptide specific immune responses by ELISPOT assay, with one additional patient falling just below the positivity threshold.
"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," said Dr. Fredrik Schjesvold, Founder and Leader of Oslo Myeloma Center at Oslo University Hospital and President of the Nordic Myeloma Study Group.
Addressing Unmet Medical Need
RAS-mutant multiple myeloma represents a significant unmet medical need, affecting an estimated 15-20% of multiple myeloma patients. These patients have poor prognosis and currently no available targeted treatment options. Oncogenic RAS mutations drive up to 30% of all cancers, making this a broadly relevant therapeutic target.
"RAS-mutant multiple myeloma has poor prognosis and there are currently no available targeted treatment options for this patient population," Dr. Schjesvold noted. The trial aims to assess whether T-cell responses to mutant RAS induced by TG01 can enhance and prolong clinical benefit in this underserved population.
Biomarker Development and Patient Selection
The genetic characteristics of patients mechanistically support the observed immune responses and clinical benefit, proposing novel biomarkers for patient selection in future trials. Dr. Victor Levitsky, Chief Scientific Officer of Circio Holding ASA, explained that "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 patient's genetic buildup."
This mechanistic validation provides important insights for optimizing patient selection in future clinical studies. The connection between patient genetics and treatment response suggests specific biomarkers could identify patients most likely to benefit from TG01 treatment.
Broader Development Strategy
The multiple myeloma results are consistent with prior observations in pancreatic cancer, where TG01 has also shown immunological activity. Circio has been awarded prestigious research grants from Innovation Norway and the Norwegian Research Council to advance the TG mutant RAS cancer vaccine program, funding two active clinical studies including the current multiple myeloma trial and a phase 2 trial at Georgetown University testing TG01 in pancreatic and lung 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. Levitsky. Circio continues to develop TG01 through external partnerships while advancing its core circular RNA technology platform.
The study continues enrollment and analysis of TG01 vaccine-specific responses, with Dr. Hanne Norseth serving as the primary investigator. Oslo University Hospital sponsors the trial, which represents an important step toward developing targeted therapies for RAS-mutant cancers.
