Metastatic or advanced solid tumors with an intermediate tumor mutational burden MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: Atezolizumab
Other descriptive name: Tecentriq
Concentration unit: mg milligram(s)
Con
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent. 2. Age = 18 years. 3. Performance status (WHO) of 0-1. 4. Histologically confirmed advanced and/or metastatic solid tumors for which standard curative measures do not exist. 5. Radiologically measurable disease according to RECIST v1.1. 6. Life expectancy estimated by the Investigator to be =12 weeks. 7. Metastatic Lesion(s) or primary tumour accessible for biopsy 8. Intermediate tumor mutational burden of 5-10 mutations/mb 9. Adequate organ function assessed by screening laboratory values: a. Absolute lymphocyte count = 0.5 x 109/L b. Neutrophils = 1.5 x 109/L c. Platelets = 100 x 109/L. For patients with primary hepatocellular carcinoma platelet counts =65 x 109/L is allowed. d. Hemoglobin = 90 g/L (5.6 mmol/L) and at least 4 weeks since blood transfusion e. Serum creatinine = 1.5 × upper limit of normal (ULN) or calculated by Cockroft-Gault formula or directly measured creatinine clearance = 50 mL/min at screening f. AST = 3 x ULN without, and = 5 x ULN with hepatic metastasis g. Bilirubin = 1.5 x ULN (except patients with Gilbert’s syndrome, who must have total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: Any of the following : 1. Pregnancy, lactation, or breastfeeding. 2. History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or anticonvulsants in the last 14 days prior to Screening. 3. Known deficiency in thiopurine methyltransferase (TPMT) or NUDT15 4. Use, or have used, any concomitant anti-cancer medications within the previous 30 days or 5 half-lives of the medication (whichever is shortest) prior to first dose (bisphosphonates, denosumab and androgen deprivation therapies such as LHRH (GnRH) agonists are allowed if patient is on stable treatment for at least 4 weeks prior to first dose). Limited field radiotherapy for palliative purpose is allowed at any time. 5. Participants with immune-related adverse events attributed to prior immunomodulatory therapy must have resolved to Grade = 1 (according to NCI CTCAE v 5.0) or baseline other than adverse events that are clinically non-significant and/or stable on supportive therapy, and are not expected to interfere with treatment in the study such as: a. Grade = 2 alopecia, asthenia, dermatologic events. b. Grade = 2 anemia if hemoglobin ? 90 g/L (5.6 mmol/L) c. Grade 2 (> 1.5-2.0 x ULN) asymptomatic amylase and/or lipase elevation with no abdominal pain and no characteristic CT findings. However, weekly monitoring of amylase and lipase is required in this case. 6. Be an organ transplant recipient. 7. Have a history of prior other malignancy (with the exception of localized prostate cancer, adequately treated basal skin cancer or carcinoma in-situ of the cervix) within 2 years prior to first dose. 8. Have a severe autoimmune disorder requiring treatment during the last 12 months prior to first dose. Diabetes on stable anti-diabetic medication, hypothyroidism and adrenocortical deficiency on stable substitution therapy are allowed. 9. Be on chronic therapy with systemic immunosuppressant medication (inhaled, intra articular and low dose systemic corticosteroids, e.g. 7.5 mg or less prednisolone per day is allowed, provided that treatment has been unchanged for at least 4 weeks prior to first dose of IMP). 10. Known HIV, active hepatitis B or hepatitis C infection. 11. Participants with a history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or known hypersensitivity to Chinese hamster ovary cell products or to any component of the Atezolizumab formulation 12. Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient’s compliance with the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: To characterize safety and tolerability of Atezolizumab given in combination with 6-thioguanine and 6-mercaptopurine Phase II: To evaluate the anti-tumor activity in terms of objective response in patients treated with Atezolizumab, 6-thioguanine and 6- mercaptopurine;Secondary Objective: To evaluate the efficacy and anti-tumor activity in patients treated with Atezolizumab given in combination with 6-thioguanine and 6-mercaptopurine;Primary end point(s): Phase 1: - Dose-limiting Toxicity according to CTCAE v5.0 - Maximum tolerated dose and/or recommended phase 2 dose Phase 2 - Objective response rate according to RECIST criteria version 1.1;Timepoint(s) of evaluation of this end point: Phase 1: Dose-limiting-toxicity evaluation period of 4 weeks Phase 2: Patients will be evaluated with relevant imaging every 9th week. (cycle 3,6,9 an subsequent every third cycle) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression Free Survival - Overall Survival - Duration of Response;Timepoint(s) of evaluation of this end point: Patients will be followed up for overall survival by yearly check of medical records until death or loss to follow up, up to two years after the end of this study. | — |
Countries
Denmark
Contacts
Public ContactKristoffer Staal Rohrberg
Rigshospitalet
Outcome results
None listed