A Phase II Study to Evaluate the Therapeutic Activity of RO6874281, an Immunocytokine, Consisting of Interleukin-2 Variant (IL-2V) Targeting Fibroblast Activation Protein-? (FAP), in Combination with Atezolizumab (Anti-PD-L1), Administered Intravenously, in Participants with Advanced and/or Metastatic Solid Tumors
- Conditions
- Advanced and/or Metastatic Solid TumorsMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003182-94-PL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 280
- Age >= 18 years
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- Eastern Cooperative Oncology Group Performance Status 0 or 1 or Karnofsky Performance Score >= 70
- Life expectancy of >= 12 weeks
- Absence of rapid disease progression or threat to vital organs or critical anatomical sites (e.g., central nervous system [CNS] metastasis, respiratory failure due to tumor compression, spinal cord compression) requiring urgent alternative medical intervention.
- Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician and the participant’s consented willingness to undergo baseline and on treatment tumor biopsies for PD biomarker analysis (not applicable to Part I Cohort A).
- Consent to provide an archival tumor tissue sample
- Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamic biomarker analysis
- Adequate cardiovascular, hematological, liver and renal function
- Adverse events related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade <= 1, except alopecia and Grade 2 peripheral neuropathy
- Participants with unilateral pleural effusion (indications other than NSCLC) are eligible if they fulfill both of the following:
a) New York Heart Association Class 1
b) Forced expiratory volume 1 and forced vital capacity >70% predicted
value; participants with lung metastases should present with Diffusing
capacity of the lungs for carbon monoxide >60 % of predicted value
- For male and female participants: The contraception and abstinence requirements are intended to prevent exposure of an embryo to the
study treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140
- Symptomatic or untreated central nervous system (CNS) metastases
- History of treated asymptomatic CNS metastases
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks before enrollment
- Leptomeningeal disease
- An active second malignancy
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or other disease with ongoing fibrosis
- Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration, including any of the following: hypertensive crisis/encephalopathy, uncontrolled hypertension, unstable angina, transient ischemic attack/stroke, congestive heart failure of any New York Heart Association classification, serious cardiac arrhythmia requiring treatment, history of thromboembolic events, hypertensive encephalopathy
- Active or uncontrolled infections
- Known Human immunodeficiency virus or active hepatitis A (HAV)
hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D (HDV) or hepatitis E (HEV) infection
- Severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- History of chronic liver disease or evidence of hepatic cirrhosis
- Dementia or altered mental status that would prohibit informed consent
- History of, active or suspicion of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- Participants with a history of autoimmune hypothyroidism on a stable dosage of thyroid replacement hormone may be eligible with approval by the Medical Monitor
- Participants with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study with approval by the Medical Monitor
- History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field is permitted
- Bilateral pleural effusion confirmed by x-ray
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Concurrent therapy with any other investigational drug
- Immunomodulating agents
- Treatment with systemic immunosuppressive medications including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to Cycle 1, Day 1
- Treatment with cytostatic drug in < 28 days prior to Cycle 1, Day 1
- Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy.
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study an
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method