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Tiragolumab and Atezolizumab for the Treatment of 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 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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 12 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2022-11-17
Primary completion: 2026-06-30
Study completion finish: 2026-06-30
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT05286801
Intervention or treatment
BIOLOGICAL: Atezolizumab
PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
OTHER: Fludeoxyglucose F-18
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Positron Emission Tomography
BIOLOGICAL: Tiragolumab
PROCEDURE: X-Ray Imaging
Conditions
- • Recurrent Malignant Solid Neoplasm
- • Recurrent Rhabdoid Tumor
- • Refractory Malignant Solid Neoplasm
- • Refractory Rhabdoid Tumor
- • Rhabdoid Tumor
- • Atypical Teratoid/Rhabdoid Tumor
- • Epithelioid Sarcoma
- • Kidney Medullary Carcinoma
- • Malignant Solid Neoplasm
- • Poorly Differentiated Chordoma
- • Recurrent Atypical Teratoid/Rhabdoid Tumor
- • Recurrent Chordoma
- • Recurrent Epithelioid Sarcoma
- • Recurrent Kidney Medullary Carcinoma
- • Refractory Atypical Teratoid/Rhabdoid Tumor
- • Refractory Chordoma
- • Refractory Epithelioid Sarcoma
- • Refractory Kidney Medullary Carcinoma
Find a site
Closest Location:
Sydney Children's Hospital
Research sites nearby
Select from list below to view details:
Sydney Children's Hospital
Randwick, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Royal Children's Hospital
Parkville, Victoria, Australia
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?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Arm B (atezolizumab, tiragolumab)
| BIOLOGICAL: Atezolizumab
|
EXPERIMENTAL: Part A (atezolizumab, tiragolumab)
| BIOLOGICAL: Atezolizumab
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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 outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Trough concentration of tiragolumab as monotherapy in cycle 1 | 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 | 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 | 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 |
Progression free survival (PFS) of the combination therapy for tiragolumab and atezolizumab | 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 | 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 | 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 |
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