A Phase II, Single-Arm, Open-Label Study Evaluating the Safety and Pharmacokinetics of the Intravenous Fixed-Dose Combination (IV FDC) of Tiragolumab and Atezolizumab in Participants With Locally Advanced, Recurrent or Metastatic Solid Tumors
Study Identifier:
GO44096
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Study Complete
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Study Summary
To assess the safety, pharmacokinetics, and immunogenicity of tiragolumab and atezolizumab intravenous fixed-dose combination (IV FDC) in participants with histologically confirmed PD-L1-selected solid tumors whose disease is locally advanced, recurrent, or metastatic and for whom an investigational agent in combination with an anti-PD-L1 antibody is considered an acceptable treatment option. To test the safety, tolerability and effects (good) of an experimental drug called tiragolumab in combination with a drug called atezolizumab in people with locally advanced or metastatic (spread to other parts of the body) cancer. or bad) and learn how the body processes both drugs. To evaluate the safety and tolerability of tiragolumab and atezolizumab intravenous (IV) fixed-dose combination (FDC)
This study will evaluate the safety, pharmacokinetics, and immunogenicity of tiragolumab and atezolizumab IV FDC (Q3W dosing) in patients with locally advanced, recurrent, or metastatic solid tumors.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Solid Tumor
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
Inclusion criteria
- 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 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 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 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) immunohistochemistry (IHC) assay
- CFDA:
- 1Sign Informed Consent Form2The person must be at least 18 years old when signing the informed consent form.3Based on the researchers' judgment, the patients were able to follow the research protocol.4An ECOG fitness score of 0 or 15Life expectancy ≥ 12 weeks6Based on the following laboratory test results obtained within 14 days prior to the start of study treatment (day 1 of cycle 1), the patient had good hematological and end-organ function.7Apart from hair loss, all acute toxicities from previous treatments have been reversed (i.e., improved to grade 1 or better).8The HIV test result was negative during screening.9The screening result for hepatitis B surface antigen (HBsAg) is negative, accompanied by any of the following: a negative result for hepatitis B core antibody (total HBcAb); or a positive result for total HBcAb followed by a negative result for hepatitis B virus (HBV) DNA.10A negative hepatitis C virus (HCV) antibody test during the screening period, or a positive HCV antibody test during the screening period followed by a negative HCV RNA test.11The EBV (Epstein-Barr virus) viral capsid antigen (VCA) IgM test was negative during the screening period.12For female subjects of fertility (including those with tubal ligation), a negative serum pregnancy test result within 14 days prior to the start of treatment (day 1 of cycle 1) was required.13For female participants of fertility: they agreed to abstain from sexual intercourse (abstaining from heterosexual intercourse) or use contraception, and agreed not to donate eggs.14For male participants: consent to abstinence (avoiding heterosexual intercourse) or condom use, and consent to avoid sperm donation.15For patients with histological records of locally advanced, recurrent, or metastatic malignant tumors who do not qualify for local radical treatment, a clinical trial combining the investigational drug with an anti-PD-L1 antibody is considered an acceptable treatment option.16Previously untreated checkpoint inhibitors (CPI-naïve), including but not limited to anti-PD-1/PD-L1, anti-CTLA-4, and anti-TIGIT.17Measurable diseases according to RECIST v1.1 criteria18Prior to enrollment, archived tumor and/or fresh tumor tissues will be submitted to the RTD central laboratory for PD-L1 evaluation.19PD-L1 positive tumors were identified using the investigational VENTANA® PD-L1 (SP263) IHC assay kit. Tumor types included: EAC, ESCC, GC, GEJ, HCC, melanoma, NSCLC, RCC, SCCHN, and UBC.20Potential subjects are eligible for enrollment in the study only if they meet all of the following specific criteria for all other indications: NSCLC: Subjects with tumors having a known sensitizing epidermal growth factor receptor (EGFR) mutation must also have experienced disease progression (during or after treatment) or be intolerant to EGFR tyrosine kinase inhibitor therapy (if available and approved by their local regulatory agency). For subjects with EGFR T790M mutation-positive NSCLC, if osimertinib is available and approved for the treatment of EGFR T790M mutation-positive NSCLC that has progressed after treatment with other EGFR tyrosine kinase inhibitors, one of those inhibitors must be osimertinib. Subjects with tumors having a known anaplastic lymphoma kinase (ALK) rearrangement must also have experienced disease progression (during or after treatment) or be intolerant to ALK tyrosine kinase inhibitor therapy (if available and approved). Subjects with tumors having a known ROS1 rearrangement must also have experienced disease progression (during or after treatment) or be intolerant to ROS1 tyrosine kinase inhibitor therapy (if available and approved). Subjects with tumors possessing the BRAFV600E mutation must also have experienced disease progression (during or after treatment) or be intolerant to dabrafenib in combination with trametinib (if available and approved). GC, GEJ, EAC, or ESCC: Subjects with type I-III GEJ tumors are eligible to participate in the study, defined as adenocarcinoma with the tumor center located within 5 cm of the anatomical esophagogastric junction (Rüdiger Siewert et al. (2000)). Subjects with HER2-positive tumors must also have experienced disease progression (during or after treatment) or be intolerant to HER2-targeting antibody/HER2 inhibitor therapy (if available and approved). SCCHN: Subjects with SCCHN tumors in the oral cavity, oropharynx, hypopharynx, or larynx, those unsuitable for radical treatment of any other major anatomical site in the head and neck, subjects with SCCHN tumors of unknown primary site, or subjects with non-squamous histological tumors are not eligible to participate in the study. The human papillomavirus (HPV) status of oropharyngeal SCCHN subjects must be known. UBC: Subjects with mixed histology, including the renal pelvis, ureter, bladder, and urethra, must have a predominantly transitional cell histology. Melanoma: Only advanced metastatic cutaneous melanoma (excluding ocular and mucosal melanoma). Subjects with tumors having a known BRAF V600E mutation must also have experienced disease progression (during or after treatment) or be intolerant to BRAF inhibitors and/or mitogen-activated protein kinase inhibitors. RCC: RCC with clear cell histological components and/or sarcomatoid histological components.
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 Known clinically significant liver disease Poorly controlled Type 2 diabetes mellitus 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 Severe infections within 4 weeks prior to Day 1 of Cycle 1 or recent infections/oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1 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 that resulted in permanent discontinuation of the prior immunotherapeutic agent and/or occurred
- CFDA:
- 1If you are pregnant or breastfeeding, or plan to become pregnant during the study period or within 5 months after the last dose of tiragolumab and atezolizumab IV FDC.2Major cardiovascular diseases, such as New York Heart Association heart disease, myocardial infarction within the past 3 months, unstable arrhythmias and/or unstable angina.3Known clinically significant liver disease, including active viral, alcoholic or other hepatitis, cirrhosis, hereditary liver disease, or current alcoholism.4Poorly controlled type 2 diabetes is defined as screening hemoglobin A1C ≥ 8% or fasting blood glucose ≥ 160 mg/dL (or 8.8 mmol/L).5Major surgery performed within 28 days prior to Day 1 of Cycle 1, or major surgery expected to be required during the study period.6Subjects must have any other disease, metabolic disorder, abnormal physical examination results and/or clinical laboratory test results, and there is reason to suspect that such disease or condition may lead to contraindication to the use of the investigational drug, affect the interpretation of study results, or put the subject at high risk of treatment complications.7A history of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, granulomatous polyangiitis, Sjögren's syndrome, Behr's palsy (autoimmune etiology only), Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.8During the two weeks prior to Day 1 of Cycle 1, patients received systemic immunosuppressive therapy (including but not limited to prednisone >10 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and tumor necrosis factor α [TNF-α] antagonist therapy).9Patients with a history of idiopathic pulmonary fibrosis, pneumonia (including drug-induced pneumonia), or tissue pneumonia (i.e., obliterative bronchiolitis, cryptogenic tissue pneumonia, etc.), or a history of radiation-induced pneumonia (fibrosis) in the radiation field found on chest computed tomography (CT) scans during the screening period, are eligible to be enrolled in the study.10Active tuberculosis11Severe infection occurring within the four weeks prior to Day 1 of Cycle 1, including but not limited to hospitalization due to complications such as infection, bacteremia, or severe pneumonia.12Recent infections that do not meet the above criteria for severe infection include: signs or symptoms of infection appearing within 2 weeks prior to Day 1 of Cycle 1; patients receiving oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1; and patients receiving prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible to participate in the study.13Previous allogeneic bone marrow transplant or previous solid organ transplant14Receive the live attenuated vaccine within 4 weeks prior to Day 1 of Cycle 1, or if you are expected to require the live attenuated vaccine during the study period.15A history of severe allergic reaction, immediate allergic reaction, or other hypersensitivity reaction to chimeric or humanized antibodies or fusion proteins.16Hypersensitivity reactions to CHO cell products are known.17Allergy or hypersensitivity to any component of tiragolumab or atezolizumab IV FDC formulation.18No anticancer treatment, whether experimental or approved, received within 3 weeks prior to the start of study treatment, including chemotherapy, hormone therapy, and/or radiation therapy, with the following exceptions: Hormone therapy with gonadotropin-releasing hormone agonists or antagonists for prostate cancer; hormone replacement therapy or oral contraceptives discontinued for more than 7 days before day 1 of cycle 1; locally approved tyrosine kinase inhibitors (TKIs) for cancer treatment; a baseline scan must be performed after discontinuation of the previous TKI, and the criteria for adverse events attributable to prior cancer treatment must be met. Treatment with traditional Chinese medicine more than 1 week before day 1 of cycle 1; palliative radiation therapy for painful metastases or metastatic lesions in potentially sensitive sites (e.g., epidural space) more than 2 weeks before day 1 of cycle 1; stereotactic radiotherapy, whole-brain radiotherapy, or neurosurgical resection for CNS metastases according to the exclusion criteria for CNS metastases.19Previous CPI treatment, including but not limited to anti-TIGIT, anti-PD-L1, anti-PD-1, and anti-CTLA.20MAb and MAb-derived therapies (excluding CPIs) must have a drug elimination half-life of less than 5 days from the last dose to day 1 of the planned cycle 1 (approximately 100 days for typical MAbs). Treatments include, but are not limited to, co-stimulatory receptor agonists and T-cell recruitment bispecific antibodies.twenty oneThe patient has a history of immunomodulatory agents with a last dose less than 6 weeks prior to day 1 of the planned first cycle. Treatment includes, but is not limited to, Toll-like receptor agonists, indoleamine 2,3-deoxygenase or tryptophan-2,3-dioxygenase inhibitors, or OXO40 agonists.twenty twoCancer vaccine and/or cytokine therapy last dose to day 1 of cycle 1 is less than 6 weeks or 5 drug elimination half-lives (whichever is shorter).twenty threeAny history of immune-mediated grade 4 adverse events attributable to prior cancer immunotherapy (excluding endocrine disorders treated with alternative therapy or asymptomatic elevation of serum amylase or lipase).twenty fourAny history of an immune-mediated grade 3 adverse event attributable to prior cancer immunotherapy and leading to permanent discontinuation of the prior immunotherapy (excluding endocrine disorders treated with replacement therapy or asymptomatic elevation of serum amylase or lipase) and/or such events occurring within ≤6 months of day 1 of cycle 1.25Any immune-mediated adverse events associated with prior cancer immunotherapy (except for endocrine disorders treated with alternative therapy or stable vitiligo) must completely resolve to baseline levels.26Except for hair loss, vitiligo, or endocrine disorders managed with replacement therapy, adverse events following previous anticancer treatment have not yet regressed to grade ≤1.27NSCLC (Neuro-SCLC) subtype of pulmonary lymphoepithelial carcinoma patients28Primary malignant tumors of the central nervous system (CNS), untreated CNS metastases, or active CNS metastases (progression or requiring corticosteroids to control symptoms).29Leptomeningeal diseases30Uncontrolled tumor-related pain31Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more).32The patient must have had other malignant tumors other than the study disease within the five years prior to Day 1 of Cycle 1, except for malignant tumors with negligible risk of metastasis or death.33Uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium ≥ULN) or symptomatic hypercalcemia requires continued bisphosphonate therapy or denosumab.34Spinal cord compression that has not undergone radical treatment with surgery and/or radiation, or previously diagnosed spinal cord compression with no clinical evidence of disease stability for ≥2 weeks prior to screening after treatment.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor