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.
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.
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
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.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.