Sponsor decision

T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)

Patients with advanced metastatic colorectal cancer who have no other effective treatment options will be offered the treatment. These patients have a poor prognosis, and there is a strong need for improved therapy.

The patients will be given adoptive cell therapy (ACT) with Radium-1 TCR+ T cells transiently redirected against the TGFβRII frameshift antigen which is expressed in MSI+ colon cancer. The first report on TCR therapy in colon cancer was targeting carcinoembryonic antigen (CEA) where some evidence of clinical response was seen, but the T-cell function may have been inhibited due to the necessity to resolve the severe colitis which occurred due to the presence of CEA in normal cells in the colon. This demonstrates the feasibility of T-cell therapy in metastatic colon cancer, but also the limitations of targeting CEA as an antigen.

Inclusion Criteria:

• Patients with metastatic colon cancer which is MSI+ with the presence of the -1A deletion in TGFβRII gene, and positive for HLA-A02 genotype
• Measurable disease
• Female or male patients. Fertile females must have a negative pregnancy test before inclusion in the trial. Both fertile men and women must be ready and able to use highly effective methods of contraception, defined as use of oral, implanted, injectable, and mechanical or barrier products for the prevention of pregnancy during participation of the trial
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
• Age 18 years and older
• Life expectancy of at least 3 months
• Signed informed consent (by the subject or subject's legal representative) obtained before any trial-related procedures.
• Adequate organ function, measured by pre-defined laboratory values

Exclusion criteria

• Other metastatic malignancies
• Any other anti-tumour treatment within 4 weeks prior to first administration of cells.
• Steroid treatment, except substitution dose
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina or serious cardiac arrhythmia
• Active infection requiring antibiotic therapy
• Pregnancy or lactation
• Known hypersensitivity to any of the components of the investigational product
• Patients who test positive for hepatitis B, C, HIV or syphilis
• Any reason why, in the opinion of the investigator, the patient should not participate