Study Stopped
Other - Protocol moved to Disapproved
Testing the Combination of Anti-cancer Drugs Tiragolumab and Atezolizumab to Improve Outcomes for Patients With Recurrent Glioblastoma
Phase 2 and Biomarker Trial of Anti-TIGIT and Anti-PDL1 in Patients With Recurrent Glioblastoma
3 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase II trial compares the safety, side effects and effectiveness of atezolizumab with tiragolumab to atezolizumab alone in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Glioblastoma is the most common primary brain cancer in adults and despite aggressive treatment, it is nearly always fatal. Currently, there are limited effective treatment options in patients that have recurrence. Immunotherapy has been shown to be effective in other types of cancer and may be an appealing potential treatment option for recurrent glioblastoma. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Study doctors also want to learn if a tumor infiltrating T lymphocyte (TIL) response is helpful to determine the benefit of the combination of study drugs compared to the usual approach. TILs are a type of immune cell that has moved from the blood into a tumor. TILs can recognize and kill tumor cells. Giving atezolizumab with tiragolumab may be safe, tolerable and/or effective compared to atezolizumab alone in treating patients with recurrent glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Apr 2025
Shorter than P25 for phase_2
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 22, 2024
CompletedFirst Posted
Study publicly available on registry
March 25, 2024
CompletedStudy Start
First participant enrolled
April 30, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2025
CompletedDecember 30, 2024
December 1, 2024
2 months
March 22, 2024
December 27, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
Will be assessed and compared between adjuvant arms. PFS will be assessed using Kaplan-Meier method.
Up to 36 months
Secondary Outcomes (8)
Tumor infiltrating T lymphocyte density
Up to 36 months
Dose limiting toxicity
Up to 30 completion of adjuvant cycle 2
Incidence of adverse events
Up to 30 days after last dose of study treatment
Objective response rate (ORR)
Up to 36 months
PFS6
At 6 months
- +3 more secondary outcomes
Other Outcomes (8)
Tumor response signatures including for T-cells, interferon and cell cycle
Up to 36 months
T cell receptor (TCR) clonality and diversity
Up to 36 months
Tumor infiltrating T-cell, T-regs, and myeloid cells
Up to 36 months
- +5 more other outcomes
Study Arms (4)
GROUP A (neoadjuvant atezolizumab, tiragolumab)
EXPERIMENTALPatients receive atezolizumab IV over 60 minutes and tiragolumab IV over 20-75 minutes and 14-19 days later, undergo surgical resection. Following surgery, patients may receive tiragolumab IV and atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study.
GROUP B (neoadjuvant tiragolumab)
EXPERIMENTALPatients receive tiragolumab IV over 20-75 minutes and 14-19 days later, undergo surgical resection. Following surgery, patients may receive tiragolumab IV and atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study.
GROUP C (neoadjuvant atezolizumab)
EXPERIMENTALPatients receive atezolizumab IV over 60 minutes and 14-19 days later, undergo surgical resection. Following surgery patients may receive atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study.
GROUP D (no neoadjuvant drug)
ACTIVE COMPARATORPatients undergo surgical resection on study. Following surgery patients may receive atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study.
Interventions
Given IV
Undergo blood sample collection
Undergo MRI
Undergo surgical resection
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed IDH wildtype World Health Organization (WHO) grade IV glioblastoma at first or second relapse
- Documented progression of disease as defined by modified Response Assessment in Neuro-Oncology (mRANO) criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with tiragolumab in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky ≥ 60%)
- Leukocytes ≥ 2,000/mcL
- Lymphocyte count ≥ 500/mcL
- Absolute neutrophil count ≥ 1,500/mcL without granulocyte colony-stimulating factor support
- Platelets ≥ 100,000/mcL without transfusion
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x institutional ULN or ≤ 5 x ULN for patients with liver metastases
- Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN for patients with documented liver or bone metastases)
- Glomerular filtration rate (GFR) ≥ 30 mL/min
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-weight heparin or warfarin, should be on a stable dose.)
- Serum albumin ≥ 2.5 g/dL
- +9 more criteria
You may not qualify if:
- Patients with IDH mutations will be excluded from the study
- Patients who have had previous treatment with anti PD1, PDL1, CTLA-4 or other immune checkpoint inhibitors
- Patients who have undergone tumor directed therapy for the most recent disease progression
- Patients who have not recovered to grade 0 or 1 or pre-treatment baseline from clinically significant adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients with a diagnosis of immunodeficiency or who require treatment with high dose systemic corticosteroids defined as dexamethasone \> 2 mg/day or bioequivalent for at least 3 consecutive days within 1 week of start of study drug
- Patients with severe, uncontrolled intercurrent illness, comorbidity, or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Patients who are pregnant or breastfeeding or are expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months after the last dose of study treatment. Women of childbearing potential (WOCPB) must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. A WOCBP who has a positive urine pregnancy test (e.g., within 72 hours) prior to treatment will be excluded from the study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Pregnant women are excluded from this study because atezolizumab and tiragolumab are monoclonal antibodies with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab and/or tiragolumab, breastfeeding should be discontinued if the mother is treated with atezolizumab and/or tiragolumab. To avoid pregnancy, WOCBPs and men must agree to use adequate contraception (i.e., contraceptive methods with a failure rate of \< 1% per year such as bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices) prior to the study, during treatment, and for 5 months after treatment ends. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Patients unable to comply with the protocol and/or not willing or who will not be available for follow-up assessments, specifically MRI scans
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the exceptions listed below:
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study
- Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- Rash must cover \< 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Megan Mantica
University of Pittsburgh Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 22, 2024
First Posted
March 25, 2024
Study Start
April 30, 2025
Primary Completion
July 1, 2025
Study Completion
July 1, 2025
Last Updated
December 30, 2024
Record last verified: 2024-12
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.