E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Solid Tumors are an abnormal mass of tissue that usually does not contain cysts or liquid areas. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the safety and tolerability of tiragolumab and atezolizumab intravenous (IV) fixed-dose combination (FDC) |
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E.2.2 | Secondary objectives of the trial |
• To characterize the pharmacokinetics of tiragolumab and atezolizumab following administration of IV FDC • To evaluate the immune response to tiragolumab and atezolizumab following IV FDC administration by measuring anti-tiragolumab and anti-atezolizumab antibodies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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 (HBcAb) - Positive 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 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 after treatment) or have an intolerance to treatment with Her2-tarageting antibody/HER2 inhibitor(s) • Participants with squamous cell carcinoma of the head and neck (SCCHN) of oral cavity, oropharynx, hypopharynx, or larynx that are inoperable. Participants with SCCHN of any other primary anatomic location in the head and neck or with SCCHN of unknown primary, or participants with tumors of non-squamous histologies are not eligible • Participants with urinary bladder cancer with mixed histologies are required to have a dominant transitional cell pattern • Participants with skin melanoma only are eligible. Those participants whose tumors have a known BRAFV600E mutation must also have experienced disease progression (during or after treatment) or have an intolerance to BRAF inhibitor(s) and/or mitogen-activated protein kinase inhibitor(s). Participants must not have received any prior cancer immunotherapy for their melanoma • Participants with renal cell carcinoma (RCC) must have a component of clear cell histology and/or component of sarcomatoid histology and not have received any other prior cancer immunotherapy for his/her cancer |
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E.4 | Principal exclusion criteria |
• 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 (~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 events from prior anti-cancer therapy that have not resolved to Grade <=1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy • Patients with the pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC • Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases • Leptomeningeal disease • Uncontrolled tumor-related pain • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures • Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1 • Uncontrolled hypercalcemia • 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 prior to screening
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 24 months |
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E.5.2 | Secondary end point(s) |
1. Area under the concentration time curve of tiragolumab and atezolizumab at Cycle 1 2. Maximum serum concentration (Cmax) of tiragolumab and atezolizumab at Cycle 1 3. Minimum serum concentration (Cmin) of tiragolumab and atezolizumab at Cycle 1 4. Prevalence of anti-drug antibodies (ADAs) to tiragolumab at baseline and the incidence of treatment emergent ADAs to tiragolumab during the study 5. Prevalence of ADAs to atezolizumab at baseline and the incidence of treatment emergent ADAs to atezolizumab during the study
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. At Cycle 1 4-5. During the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
United States |
Serbia |
Croatia |
Cyprus |
Greece |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS or the date at which the last data point required for statistical analysis (i.e., participant survival analyses) or safety follow-up is received from the last participant, whichever occurs later.
The end of the study is expected to occur 24 months after the last participant is enrolled. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |