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

April 16, 2024 updated by: National Cancer Institute (NCI)

A Phase 1/2 Study of Tiragolumab (NSC# 827799) and Atezolizumab (NSC# 783608) in Patients With Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors

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 that has either come back (relapsed) or does 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 assess the association of response rate to somatic genetic mutations of SMARCB1 or SMARCA4 and PD-L1 expression.

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 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 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.

Study Type

Interventional

Enrollment (Estimated)

86

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • Queensland Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 61 7 3068 1111
        • Principal Investigator:
          • Christopher J. Fraser
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • Hospital for Sick Children
        • Contact:
        • Principal Investigator:
          • Daniel A. Morgenstern
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Recruiting
        • Centre Hospitalier Universitaire Sainte-Justine
        • Principal Investigator:
          • Monia Marzouki
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Children's Hospital of Alabama
        • Contact:
        • Principal Investigator:
          • Girish Dhall
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:
          • Site Public Contact
          • Phone Number: 323-361-4110
        • Principal Investigator:
          • Fariba Navid
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County
        • Contact:
        • Principal Investigator:
          • Josephine H. Haduong
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Lucile Packard Children's Hospital Stanford University
        • Contact:
        • Principal Investigator:
          • Lianna J. Marks
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Medical Center-Mission Bay
        • Contact:
        • Principal Investigator:
          • Kieuhoa T. Vo
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
        • Contact:
        • Principal Investigator:
          • Margaret E. Macy
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center
        • Principal Investigator:
          • AeRang Kim
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta - Egleston
        • Contact:
        • Principal Investigator:
          • Jason R. Fangusaro
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Lurie Children's Hospital-Chicago
        • Contact:
          • Site Public Contact
          • Phone Number: 773-880-4562
        • Principal Investigator:
          • Elizabeth A. Sokol
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children
        • Contact:
          • Site Public Contact
          • Phone Number: 800-248-1199
        • Principal Investigator:
          • Melissa K. Bear
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Christine A. Pratilas
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Principal Investigator:
          • Mary F. Wedekind Malone
        • Contact:
          • Site Public Contact
          • Phone Number: 800-411-1222
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Steven G. DuBois
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • C S Mott Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Rajen Mody
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota/Masonic Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 612-624-2620
        • Principal Investigator:
          • Emily G. Greengard
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
          • Site Public Contact
          • Phone Number: 816-302-6808
          • Email: rryan@cmh.edu
        • Principal Investigator:
          • Kevin F. Ginn
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Shalini Shenoy
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Luca Szalontay
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Julia L. Glade Bender
      • Valhalla, New York, United States, 10595
        • Recruiting
        • New York Medical College
        • Principal Investigator:
          • Mitchell S. Cairo
        • Contact:
          • Site Public Contact
          • Phone Number: 914-594-3794
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 888-275-3853
        • Principal Investigator:
          • Lars M. Wagner
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Joseph G. Pressey
      • Columbus, Ohio, United States, 43205
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Bill H. Chang
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Theodore W. Laetsch
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Children's Hospital of Pittsburgh of UPMC
        • Contact:
        • Principal Investigator:
          • Andrew Bukowinski
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • Saint Jude Children's Research Hospital
        • Contact:
        • Principal Investigator:
          • Jessica Gartrell
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
        • Principal Investigator:
          • Scott C. Borinstein
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Laura J. Klesse
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 713-798-1354
          • Email: burton@bcm.edu
        • Principal Investigator:
          • Jennifer H. Foster
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Recruiting
        • Primary Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 801-585-5270
        • Principal Investigator:
          • Matthew Dietz
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 866-987-2000
        • Principal Investigator:
          • Katherine G. Tarlock
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Hospital of Wisconsin
        • Contact:
        • Principal Investigator:
          • Sarah Rumler

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation 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: 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 either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
  • 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; >= 150 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/gender 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 girls who are post-menarchal. 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 stem cell transplant are not eligible

  • Patients with known, untreated CNS metastases will be excluded with the following exceptions:

    • Patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows no evidence for active disease in the CNS
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm B (atezolizumab, tiragolumab)
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 blood sample collection on study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Biological: Atezolizumab
Given IV
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
Procedure: Computed Tomography
Undergo CT and/or PET-CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Other: Fludeoxyglucose F-18
Given FDG
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Procedure: Positron Emission Tomography
Undergo PET-CT and/or FDG-PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Biological: Tiragolumab
Given IV
Other Names:
  • MTIG7192A
  • RG6058
Procedure: X-Ray Imaging
Undergo x-rays
Other Names:
  • Conventional X-Ray
  • Diagnostic Radiology
  • Medical Imaging, X-Ray
  • Radiographic Imaging
  • Radiography
  • RG
  • Static X-Ray
  • X-Ray
  • Plain film radiographs
  • Radiographic imaging procedure (procedure)
Experimental: Part A (atezolizumab, tiragolumab)
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 blood sample collection on study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Biological: Atezolizumab
Given IV
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
Procedure: Computed Tomography
Undergo CT and/or PET-CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Other: Fludeoxyglucose F-18
Given FDG
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Procedure: Positron Emission Tomography
Undergo PET-CT and/or FDG-PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Biological: Tiragolumab
Given IV
Other Names:
  • MTIG7192A
  • RG6058
Procedure: X-Ray Imaging
Undergo x-rays
Other Names:
  • Conventional X-Ray
  • Diagnostic Radiology
  • Medical Imaging, X-Ray
  • Radiographic Imaging
  • Radiography
  • RG
  • Static X-Ray
  • X-Ray
  • Plain film radiographs
  • Radiographic imaging procedure (procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of cycle 1 dose limiting toxicities of tiragolumab as monotherapy in pediatric patients
Time Frame: Up to 21 days
Frequency (%) of pediatric patients (<18 years) with cycle 1 dose limiting toxicities attributable to tiragolumab as monotherapy in the safety cohort (Part A).
Up to 21 days
Frequency of objective response for the combination of tiragolumab and atezolizumab
Time Frame: Up to 5 years
Frequency (%) of patients with best objective response of partial or complete for the combination of tiragolumab and atezolizumab stratified by disease cohort (Part B).
Up to 5 years
Frequency of cycle 1 dose limiting toxicities of the combination of tiragolumab and atezolizumab in patients < 12 years
Time Frame: Up to 21 days
Frequency (%) of patients < 12 years with cycle 1 dose limiting toxicities attributable to the combination of tiragolumab and atezolizumab in Part B.
Up to 21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) of the combination therapy for tiragolumab and atezolizumab
Time Frame: Up to 5 years
Median (95% CI) progression-free survival for the combination therapy of tiragolumab and atezolizumab stratified by disease cohort in Part B.
Up to 5 years
Overall survival (OS) of the combination therapy for tiragolumab and atezolizumab
Time Frame: Up to 5 years
Median (95% CI) for the combination therapy of tiragolumab and atezolizumab stratified by disease cohort in Part B.
Up to 5 years
Duration of response of the combination therapy for tiragolumab and atezolizumab
Time Frame: Up to 5 years
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.
Up to 5 years
Trough concentration of tiragolumab as monotherapy in cycle 1
Time Frame: Up to 21 days
Median (min, max) of trough concentration for tiragolumab as monotherapy in cycle 1 of Part A safety cohort patients (< 18 years).
Up to 21 days
Trough concentration for tiragolumab when given in combination with atezolizumab in cycle 2, day 1
Time Frame: Up to 21 days
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.
Up to 21 days
Trough concentration for atezolizumab when given in combination tiragolumab with in cycle 3, day 1
Time Frame: Up to 21 days
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.
Up to 21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Mary F Wedekind Malone, Pediatric Early Phase Clinical Trial Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2022

Primary Completion (Estimated)

September 30, 2025

Study Completion (Estimated)

September 30, 2025

Study Registration Dates

First Submitted

March 15, 2022

First Submitted That Met QC Criteria

March 15, 2022

First Posted (Actual)

March 18, 2022

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2022-01992 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UM1CA228823 (U.S. NIH Grant/Contract)
  • PEPN2121 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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