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Active Not RecruitingNCT05286801

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

Status
Active Not Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
86 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
12 Months
Healthy volunteers
Not accepted

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.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAtezolizumabGiven IV
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREComputed TomographyUndergo CT and/or PET-CT
PROCEDUREEchocardiography TestUndergo ECHO
OTHERFludeoxyglucose F-18Given FDG
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREPositron Emission TomographyUndergo PET-CT and/or FDG-PET
BIOLOGICALTiragolumabGiven IV
PROCEDUREX-Ray ImagingUndergo x-rays

Timeline

Start date
2022-11-17
Primary completion
2030-03-31
Completion
2030-03-31
First posted
2022-03-18
Last updated
2026-04-13

Locations

40 sites across 3 countries: United States, Australia, Canada

Regulatory

Source: ClinicalTrials.gov record NCT05286801. Inclusion in this directory is not an endorsement.