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

Phase 1

Conditions: Advanced and/or Metastatic Solid Tumors
MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-003182-94-DE

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

Inclusion Criteria

- 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

Exclusion Criteria

- 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
antiphospholipid 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

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

Related Trials