Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
A Phase 1/2 Study of Tiragolumab (NSC# 827799) and Atezolizumab (NSC# 783608) in Patients With Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
3 other identifiers
interventional
86
3 countries
40
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2022
Longer than P75 for phase_1
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2022
CompletedFirst Posted
Study publicly available on registry
March 18, 2022
CompletedStudy Start
First participant enrolled
November 17, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2030
April 13, 2026
January 1, 2026
7.4 years
March 15, 2022
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Frequency of cycle 1 dose limiting toxicities of tiragolumab as monotherapy in pediatric patients
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
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
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 Outcomes (6)
Trough concentration of tiragolumab as monotherapy in cycle 1
Up to 21 days
Trough concentration for tiragolumab when given in combination with atezolizumab in cycle 2, day 1
Up to 21 days
Trough concentration for atezolizumab when given in combination tiragolumab with in cycle 3, day 1
Up to 21 days
Progression free survival (PFS) of the combination therapy for tiragolumab and atezolizumab
Up to 5 years
Overall survival (OS) of the combination therapy for tiragolumab and atezolizumab
Up to 5 years
- +1 more secondary outcomes
Study Arms (2)
Arm B (atezolizumab, tiragolumab)
EXPERIMENTALPatients 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.
Part A (atezolizumab, tiragolumab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo CT and/or PET-CT
Undergo x-rays
Undergo blood sample collection
Undergo ECHO
Given FDG
Undergo MRI
Undergo PET-CT and/or FDG-PET
Given IV
Eligibility Criteria
You may qualify if:
- 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
- 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
- +43 more criteria
You may not qualify if:
- 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
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (40)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
New York Medical College
Valhalla, New York, 10595, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mary F Wedekind Malone
Pediatric Early Phase Clinical Trial Network
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2022
First Posted
March 18, 2022
Study Start
November 17, 2022
Primary Completion (Estimated)
March 31, 2030
Study Completion (Estimated)
March 31, 2030
Last Updated
April 13, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
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.