To Evaluate the Safety and Pharmacokinetics of the Intravenous Fixed dose Combination (IV FDC) OfTiragolumab and Atezolizumab in Participants with Locally Advanced, Recurrent or Metastatic Solid Tumors
- Conditions
- Solid TumorsMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-001157-23-GR
- Lead Sponsor
- F.Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
• Age >=18 years at the time of signing Informed Consent Form
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy >=12 weeks
• Adequate hematologic and end organ function
• Recovery (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Positive hepatitis B surface antibody (HBsAb) test at screening, or a negative HBsAb at screening accompanied by either of the following:
- Negative hepatitis B core antibody (total HBcAb)
- Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test
• Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening
• Negative Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgM test during screening
• For female participants of childbearing potential, negative serum pregnancy test within 14 days prior to initiation of study treatment (Day 1 of Cycle 1)
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs during the treatment period and for 5 months after the final dose of tiragolumab and atezolizumab IV FDC
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of tiragolumab and atezolizumab IV FDC to avoid exposing the embryo
Cancer-Specific Inclusion Criteria:
• Histologic documentation of locally advanced, recurrent, or metastatic malignancy for which a clinical trial of an investigational agent in combination with an anti-PD-L1 antibody is considered an acceptable treatment option. Participant must be informed of all standard of care options available for his/her cancer.
• No prior treatment with checkpoint inhibitor therapies (CPI-Naive)
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Submittal of archival tumor and/or fresh tumor tissue to the RTD central laboratory for programmed death-1 (PD-L1) evaluation prior to enrollment
• PD-L1 selected tumors, as determined by the investigational VENTANA PD-L1 (SP263) IHC assay
Additional Inclusion Criteria for Indication-Specific Cancer:
• Non-small cell lung cancer (NSCLC): Participants whose tumors have a known sensitizing epidermal growth factor receptor (EGFR) mutation must also have experienced disease progression (during or after treatment) or have an intolerance to treatment with an EGFR tyrosine kinase inhibitor(s). Participants with EGFR T790M mutation positive NSCLC, one of those EGFR tyrosine kinase inhibitors must have been osimertinib if approved by local regulatory authorities for treatment of EGFR T790 mutation positive NSCLC after progression on other EGFR tyrosine inhibitors
• Gastroesophageal junction cancer (GEJ) or EAC or esophageal squamous cell carcinoma (ESCC): Participants with Type 1 GEJ tumor, defined as adenocarcinoma of the distal esophagus with the tumor center located within 1 to 5 cm above the anatomic esophagogastric junction, are eligible for the study. Participants whose tumors are HER2-positive must have experienced disease progression (during or a
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of tiragolumab and atezolizumab IV FDC
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, and/or unstable angina
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse
• Poorly controlled Type 2 diabetes mellitus, defined as a screening hemoglobin A1C >=8% or a fasting plasma glucose >=160 mg/dL
• Major surgical procedure within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study
• Any other diseases, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the participant at high risk from treatment complications
• History of autoimmune disease
• Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1 of Cycle 1
• History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Active tuberculosis
• Severe infections within 4 weeks prior to Day 1 of Cycle 1
• Recent infections not meeting the above criteria for severe infections, including the following:
- Signs or symptoms of infection within 2 weeks prior to Day 1 of Cycle 1
- Received oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
- Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Administration of a live, attenuated vaccine within 4 weeks before Day 1 of Cycle 1 or anticipation that such a live attenuated vaccine will be required during the study
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to CHO-cell products
• Allergy or hypersensitivity to components of the atezolizumab and tiragolumab IV FDC formulation
Cancer-Specific Exclusion Criteria:
• Any anti-cancer therapy, whether investigational or approved within 3 weeks prior to initiation of study treatment
• Prior treatment with immune checkpoint inhibitors (CPIs)
• Less than 5 drug-elimination half-lives (approximately ~100 days for typical monoclonal antibody [Mab]) from the last dose of monoclonal antibodies (MAbs), and MAb-Derived Therapies (excluding CPIs) and the proposed Day 1 of Cycle 1
• Less than 6 weeks between the last dose of prior immunomodulators and the proposed Day 1 of Cycle 1
• Less than 6 weeks or 5-drug-elimination half-lives, whichever is shorter, of prior treatment with cancer vaccines and/or cytokines have elapsed between the last dose and the proposed Cycle 1, Day 1
• Any history of an immune-mediated Grade 4 adverse event attributed to prior cancer immunotherapy
• Any history of an immune-mediated Grade 3 adverse event attributed to prior cancer immunotherapy
• Any immune-mediated adverse events related to prior cancer immunotherapy
• Adverse
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