Skip to content
Triangle logo TriangleGet started
← Study library

NCT05286801 · CITED IN SOURCE DOCUMENTS

Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1, PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-07-14

This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit * The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion * Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation in the tumor from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies: * Renal medullary carcinoma * Malignant rhabdoid tumor (extra-CNS) * Atypical teratoid rhabdoid tumor (CNS) * Poorly differentiated chordoma * Epithelioid sarcoma * Other SMARCB1 or SMARCA4 deficient tumors * Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system * Part A: Patients must have either measurable or evaluable disease Part B: Patients must have measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors * Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease * Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment * \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment * Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1 * Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Stem cell infusions (with or without total-body irradiation \[TBI\]): * Autologous stem cell infusion including boost infusion: \>= 30 days * Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) * External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation * Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy * Patients must not have had prior TIGIT targeting therapy * Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137) * Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment * Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions: * The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable * The use of topical, inhaled, or ophthalmic corticosteroids are acceptable * The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable * Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment * For patients with solid tumors without known bone marrow involvement * Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment) * For patients with solid tumors without known bone marrow involvement * Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment) * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity * A creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment): * Age; Maximum Serum Creatinine (mg/dL) * 1 to \< 2 years; Male: 0.6; Female: 0.6 * 2 to \< 6 years; Male: 0.8; Female: 0.8 * 6 to \< 10 years; Male: 1; Female: 1 * 10 to \< 13 years; Male: 1.2; Female: 1.2 * 13 to \< 16 years; Male: 1.5; Female: 1.4 * \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment) * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment) * Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN * Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L * Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment) * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days * Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible * International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment) * Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment) * Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment) * Grade 1 or lower calcium level * Note: can have history of hypercalcemia as long as controlled and asymptomatic Exclusion Criteria: * Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control. * It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later * Concomitant medications: * Corticosteroids: * Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions: * The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable * The use of topical, inhaled, or ophthalmic corticosteroids are acceptable * The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable * Investigational drugs: Patients who are currently receiving another investigational drug are not eligible * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible * Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible * Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection * History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins * Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation * Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible * Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS. * Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate * Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible * Patients who have active immune deficiency are not eligible * Patients who have known active tuberculosis are not eligible * Hepatitis B or C infection: * Patients \< 18 years old at enrollment, who have known hepatitis B or C * Patients \>= 18 years old at enrollment with: * Positive hepatitis B surface antigen (HBsAg), OR * Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR * Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test * Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test * Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible * Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load * Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible * Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible * Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted * Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed * Patients who have an uncontrolled infection are not eligible * Patients who have received a prior solid organ transplantation are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
healthy Volunteers
false
minimum Age
12 Months
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive atezolizumab IV over 30-60 minutes on day 1 and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.
    intervention Names
    1. Biological: Atezolizumab
    2. Procedure: Biospecimen Collection
    3. Procedure: Computed Tomography
    4. Other: Fludeoxyglucose F-18
    5. Procedure: Magnetic Resonance Imaging
    6. Procedure: Positron Emission Tomography
    7. Biological: Tiragolumab
    8. Procedure: X-Ray Imaging
    label
    Arm B (atezolizumab, tiragolumab)
    type
    EXPERIMENTAL
  2. description
    Patients receive tiragolumab IV over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.
    intervention Names
    1. Biological: Atezolizumab
    2. Procedure: Biospecimen Collection
    3. Procedure: Computed Tomography
    4. Procedure: Echocardiography Test
    5. Other: Fludeoxyglucose F-18
    6. Procedure: Magnetic Resonance Imaging
    7. Procedure: Positron Emission Tomography
    8. Biological: Tiragolumab
    9. Procedure: X-Ray Imaging
    label
    Part A (atezolizumab, tiragolumab)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Given IV
    name
    Atezolizumab
    other Names
    1. MPDL 3280A
    2. MPDL 328OA
    3. MPDL-3280A
    4. MPDL3280A
    5. MPDL328OA
    6. RG 7446
    7. RG-7446
    8. RG7446
    9. RO 5541267
    10. RO-5541267
    11. RO5541267
    12. Tecentriq
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Undergo blood sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Sample Collection
    4. Specimen Collection
    type
    PROCEDURE
  3. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Undergo CT and/or PET-CT
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. Diagnostic CAT Scan
    11. Diagnostic CAT Scan Service Type
    12. tomography
    type
    PROCEDURE
  4. arm Group Labels
    1. Part A (atezolizumab, tiragolumab)
    description
    Undergo ECHO
    name
    Echocardiography Test
    other Names
    1. EC
    2. Echocardiography
    type
    PROCEDURE
  5. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Given FDG
    name
    Fludeoxyglucose F-18
    other Names
    1. 18FDG
    2. FDG
    3. Fludeoxyglucose (18F)
    4. fludeoxyglucose F 18
    5. Fludeoxyglucose F18
    6. Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    7. Fluorodeoxyglucose F18
    type
    OTHER
  6. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Undergo MRI
    name
    Magnetic Resonance Imaging
    other Names
    1. Magnetic Resonance
    2. Magnetic Resonance Imaging (MRI)
    3. Magnetic resonance imaging (procedure)
    4. Magnetic Resonance Imaging Scan
    5. Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    6. MR
    7. MR Imaging
    8. MRI
    9. MRI Scan
    10. MRIs
    11. NMR Imaging
    12. NMRI
    type
    PROCEDURE
  7. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Undergo PET-CT and/or FDG-PET
    name
    Positron Emission Tomography
    other Names
    1. Medical Imaging, Positron Emission Tomography
    2. PET
    3. PET Scan
    4. Positron emission tomography (procedure)
    5. Positron Emission Tomography Scan
    6. Positron-Emission Tomography
    7. PT
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Given IV
    name
    Tiragolumab
    other Names
    1. MTIG7192A
    2. RG6058
    type
    BIOLOGICAL
  9. arm Group Labels
    1. Arm B (atezolizumab, tiragolumab)
    2. Part A (atezolizumab, tiragolumab)
    description
    Undergo x-rays
    name
    X-Ray Imaging
    other Names
    1. Conventional X-Ray
    2. Diagnostic Radiology
    3. Medical Imaging, X-Ray
    4. Plain film radiographs
    5. Radiographic Imaging
    6. Radiographic imaging procedure (procedure)
    7. Radiography
    8. RG
    9. Static X-Ray
    10. X-Ray
    type
    PROCEDURE
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
86
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Frequency (%) of pediatric patients (\<18 years) with cycle 1 dose limiting toxicities attributable to tiragolumab as monotherapy in the safety cohort (Part A).
    measure
    Frequency of cycle 1 dose limiting toxicities of tiragolumab as monotherapy in pediatric patients
    time Frame
    Up to 21 days
  2. description
    Frequency (%) of patients with best objective response of partial or complete for the combination of tiragolumab and atezolizumab stratified by disease cohort (Part B).
    measure
    Frequency of objective response for the combination of tiragolumab and atezolizumab
    time Frame
    Up to 5 years
  3. description
    Frequency (%) of patients \< 12 years with cycle 1 dose limiting toxicities attributable to the combination of tiragolumab and atezolizumab in Part B.
    measure
    Frequency of cycle 1 dose limiting toxicities of the combination of tiragolumab and atezolizumab in patients < 12 years
    time Frame
    Up to 21 days
secondary Outcomes
  1. description
    Median (min, max) of trough concentration for tiragolumab as monotherapy in cycle 1 of Part A safety cohort patients (\< 18 years).
    measure
    Trough concentration of tiragolumab as monotherapy in cycle 1
    time Frame
    Up to 21 days
  2. description
    Median (min, max) of trough concentration for tiragolumab when given in combination with atezolizumab in cycle 2, day 1 of Part B cohorts stratified by age group (\< 18 versus \>= 18 years) and disease cohort.
    measure
    Trough concentration for tiragolumab when given in combination with atezolizumab in cycle 2, day 1
    time Frame
    Up to 21 days
  3. description
    Median (min, max) of trough concentration for atezolizumab when given in combination tiragolumab in cycle 3, day 1 of Part B cohorts stratified by age group (\< 18 versus \>= 18 years) and disease cohort.
    measure
    Trough concentration for atezolizumab when given in combination tiragolumab with in cycle 3, day 1
    time Frame
    Up to 21 days
  4. description
    Median (95% CI) progression-free survival for the combination therapy of tiragolumab and atezolizumab stratified by disease cohort in Part B.
    measure
    Progression free survival (PFS) of the combination therapy for tiragolumab and atezolizumab
    time Frame
    Up to 5 years
  5. description
    Median (95% CI) for the combination therapy of tiragolumab and atezolizumab stratified by disease cohort in Part B.
    measure
    Overall survival (OS) of the combination therapy for tiragolumab and atezolizumab
    time Frame
    Up to 5 years
  6. description
    Median (min, max) duration of response among patients in Part B with partial or complete response to combination therapy for tiragolumab and atezolizumab stratified by disease cohort.
    measure
    Duration of response of the combination therapy for tiragolumab and atezolizumab
    time Frame
    Up to 5 years
Full study description
brief Summary
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of tiragolumab as monotherapy in pediatric patients (\< 18 years) with SMARCB1 or SMARCA4 deficient tumors. (Part A) II. To evaluate antitumor activity of the combination of tiragolumab and atezolizumab as assessed by objective response rate in patients with SMARCB1 or SMARCA4 deficient tumors per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 (for non-central nervous system \[CNS\] tumors) or CNS response criteria (for CNS tumors). (Part B) III. To evaluate the safety and adverse event profile of this combination therapy in subjects with SMARCB1 or SMARCA4 deficient tumors, with a particular focus in pediatric patients \< 12 years of age. SECONDARY OBJECTIVES: I. To characterize the pharmacokinetics of tiragolumab alone in part A and tiragolumab and atezolizumab (part A and B) when given in combination in pediatric, AYA (adolescents and young adults), and adult patients. II. To estimate the PFS (progression free survival), OS (overall survival), and duration of response of combination tiragolumab and atezolizumab in patients with SMARCB1 or SMARCA4 deficient tumors. EXPLORATORY OBJECTIVES: I. To evaluate molecular features of the SMARCB1 or SMARCA4 tumors including genomic and transcriptomic evaluation and if feasible, assess their association to clinical response. II. To assess the association of response rate to the molecular subtypes of rhabdoid/atypical teratoid rhabdoid tumor (ATRT). III. To assess changes in circulating and tumoral immune markers in patients treated with this combination therapy and correlate to response when feasible. OUTLINE: Patients are assigned to Part A or Part B. PART A: Patients receive tiragolumab intravenously (IV) over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)-CT throughout the trial. Patients also undergo echocardiography (ECHO) during screening and blood sample collection on study. PART B: Patients receive atezolizumab IV over 30-60 minutes on day 1 and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study. After completion of study treatment, patients are followed up at months 3, 6, 9, 12, 18, 24, 36, 48, and 60, up to 5 years.
Source references
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-0db1f7b64c378641727b
      requested nct id
      NCT05286801
      primary nct id
      NCT05286801
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      7560562e3838a569c94818184be048e24ff1d3f34994727e28e5a8e47d66f28e
      payload sha256
      8b1d3648b9f2f9665d3b32bdc8b8de48257dc2235416a6d5f44e2f4966a1f171
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-0db1f7b64c378641727b
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05286801
      occurrences
      1. context exact
        /or institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1238"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        546420
        exact text
        NCT05286801
        start
        546409
      2. context exact
        cal trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1238"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        546443
        exact text
        NCT05286801
        start
        546432
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/21c44e98d92c4ee887.html
      source file sha256
      7560562e3838a569c94818184be048e24ff1d3f34994727e28e5a8e47d66f28e
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:51.520868+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      dcea2437ffe21206fe0448d1b99b68926b02cc4dd28e304c48dca82a54bfd1fb
      source title
      Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 15, 2025
        datetime
        2025-04-15T12:00:00Z
        display
        April 15, 2025
    2. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-0fd267c1208c6df18f8f
      requested nct id
      NCT05286801
      primary nct id
      NCT05286801
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      394dfc4b7dae5f7cd973d88cc17da7d5870cd54097ed5255aa3d9297ded3ad36
      payload sha256
      77783219d9c9e425bd10c3d40a97c59633d5cc889e7333fc5f4a798ecedf1c92
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-0fd267c1208c6df18f8f
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05286801
      occurrences
      1. context exact
        nal and/or institutional clinical trial that is currently being conducted:</p><div class="pdq-content-list"><ul id="_2011"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        61023
        exact text
        NCT05286801
        start
        61012
      2. context exact
        l clinical trial that is currently being conducted:</p><div class="pdq-content-list"><ul id="_2011"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        61046
        exact text
        NCT05286801
        start
        61035
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/5f7d66a889d2594a0b.html
      source file sha256
      394dfc4b7dae5f7cd973d88cc17da7d5870cd54097ed5255aa3d9297ded3ad36
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:29.998188+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      a75ea7ac3ed5b17927a9665b622acc48dc6f19b180475f8302e3eb8e57308bd8
      source title
      Childhood Chordoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 3, 2025
        datetime
        2025-04-03T12:00:00Z
        display
        April 3, 2025
    3. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-28867ec4359152171022
      requested nct id
      NCT05286801
      primary nct id
      NCT05286801
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      89f1fea69338b25ed79441abc85699fd3baad3bd8b4175dc78373d152d94ef0e
      payload sha256
      f7ba5aa65243fcf38ca1873e37cf4d197d5f5925071559b167821ad3c85ea6dd
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-28867ec4359152171022
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05286801
      occurrences
      1. context exact
        d/or institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_168"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        99246
        exact text
        NCT05286801
        start
        99235
      2. context exact
        ical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_168"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        99269
        exact text
        NCT05286801
        start
        99258
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/24b3780c92327718bc.html
      source file sha256
      89f1fea69338b25ed79441abc85699fd3baad3bd8b4175dc78373d152d94ef0e
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:32.334782+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      96e2568fa482bb1f28b808634ef4b481c3cf1f460d65f41550e82c3f657c1294
      source title
      Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: March 3, 2025
        datetime
        2025-03-03T12:00:00Z
        display
        March 3, 2025
    4. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-7907b4f4bb5ff4745166
      requested nct id
      NCT05286801
      primary nct id
      NCT05286801
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      48980f570e68ac05554d63c0aab3e9a58312dca766706a01bc3307ef4abaa12b
      payload sha256
      8db343b18a63fa151b05c80527e57c28269e7304c86e76201aff9a55d2ad2aab
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-7907b4f4bb5ff4745166
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05286801
      occurrences
      1. context exact
        nal and/or institutional clinical trial that is currently being conducted:</p><div class="pdq-content-list"><ul id="_1978"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        75106
        exact text
        NCT05286801
        start
        75095
      2. context exact
        l clinical trial that is currently being conducted:</p><div class="pdq-content-list"><ul id="_1978"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        75129
        exact text
        NCT05286801
        start
        75118
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/dd6a61f635a55a026c.html
      source file sha256
      48980f570e68ac05554d63c0aab3e9a58312dca766706a01bc3307ef4abaa12b
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:09.367689+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      e75730fde4c3ac44be6f193ba7d0e25375d2e1bcf507c0e4e88bf09dea692ce2
      source title
      Childhood Ovarian Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: March 3, 2025
        datetime
        2025-03-03T12:00:00Z
        display
        March 3, 2025
    5. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-c8e33b996a985fb0f10e
      requested nct id
      NCT05286801
      primary nct id
      NCT05286801
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      087ef9142c0aebb539f4c900d83a659f1a22cd99367785543c73dbdf79e0b0cc
      payload sha256
      38a810a4bd677838bb4c85dc4bab07badcfa96450a26e6c202c8713b99ed8982
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-c8e33b996a985fb0f10e
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05286801
      occurrences
      1. context exact
        r institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_2405"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        537031
        exact text
        NCT05286801
        start
        537020
      2. context exact
        l trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_2405"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        537054
        exact text
        NCT05286801
        start
        537043
      3. context exact
        r institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1263"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class
        end
        582104
        exact text
        NCT05286801
        start
        582093
      4. context exact
        l trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1263"><li><strong><a href="/clinicaltrials/NCT05286801">PEPN2121 (NCT05286801)</a></strong> (Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory <em class="gene-name">SMARCB1</em>- or <em class="gene-name">SMARCA4</e
        end
        582127
        exact text
        NCT05286801
        start
        582116
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/a528455ae29adeef13.html
      source file sha256
      087ef9142c0aebb539f4c900d83a659f1a22cd99367785543c73dbdf79e0b0cc
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:19.581631+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      c913a60878c18e616f39a4e354327dd9ca49d6f2b8e7e636a26ce81aa9170d23
      source title
      Childhood Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 21, 2025
        datetime
        2025-04-21T12:00:00Z
        display
        April 21, 2025

    Preserved source evidence · Not medical advice