Brief Summary
This phase II study will explore the effect of 2 monoclonal antibodies, tiragolumab and atezolizumab, in patients with locally advancedat a late stage, far along solid cancers which cannot be removed by surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence or have spread. Their cancers will have characteristics which may predict immune response to the study treatment. PD-L1 and TIGIT are immune receptors which can help cancers grow by evading the immune response and inhibiting the action of some immune cellsthe basic structural and functional unit of all living things. By blocking these receptors, tiragolumab and atezolizumab may work together to re-activate the body’s anti-tumour immune response and kill cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs cells.
Intervention / Treatment
- Biological: Tiragolumab
- Biological: Atezolizumab
Inclusion Criteria:
- Provision of written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
- Aged ≥18 years old.
- Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumoura tissue mass that forms from groups of unhealthy cells.
- Exhausted all available standard therapy or not suitable for standard therapy (including targeted therapies) for the tumour.
- ECOG performance status score of 0-1.
- Sufficient and accessible tumour tissuea group of cells that work together to perform a function for panel sequencing, PD-L1 and TIL testing, and tertiary objectives.
- Tumour biomarker criteria predictive of immune response defined by presence of one or more of the following;
- Group 1: tumour mutation burden ≥ 10 mutations per megabase.
- Group 2: PD-L1 amplification >6 copy number alterations
- Group 3: tumour PD-L1 expression TAP score ≥ 5%
- Group 4: tumour infiltrating lymphocytes (TILs) (CD3+CD8+) ≥ 5%.
- Patient is willing to provide tumour biopsyremoval of a section of tissue to analyse for cancer cells samples on treatment at Week 4.
- Life expectancy >12 weeks.
- Measurable disease as defined by iRECIST or RANO criteria.
- Adequate haematological and biochemical indices as defined by:
- Absolute neutrophil count ≥1.0 x 10^9/L
- Haemoglobin ≥100 g/L
- Platelet count ≥100 x 10^9/L
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathologythe study of disease), who will be allowed only in consultation with their physician.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN; or ≤5.0x ULN if liver metastases are present.
- International normalised ratio (INR) <1.3 in the absence of anticoagulation therapy.
- Serum creatinine clearance >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
- Negative HIV test at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count ≥ 200cells/mm3 , and have an undetectable viral load.
- Negative hepatitis B surface antigen (HBsAg) test at screening.
- Positive hepatitis B surface antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:
- Negative total hepatitis B core antibody (HBcAb);
- Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL.
The HBV DNA test must be performed for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
- Women of childbearing potential must have a negative screening serum pregnancy test within 14 days prior to the first dosethe amount of medication taken of study medication.
- Women of childbearing potential and men must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the study and for at least 5 months after the last dose of study medication.
- Ability to adhere to the study visit schedule and understand and comply with all protocol requirements and instructions from study staff.