Tislelizumab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for Bevacizumab Refractory Recurrent Glioblastoma

NCT05540275 | Not Yet Recruiting Phase 2

• 1 other identifier: HenanPPH-Recurrent GBM
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the clinical efficacy and safety of Tislelizumab (one anti-PD-1 antibody same as nivolumab approved in China) in combination with bevacizumab in patients with recurrent or progressive glioblastoma (GBM) who have progressed on bevacizumab with or without PTEN or TERT gene mutations.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Overall response rate

  Proportion of participants in the analysis population who have complete response (CR) or partial response (PR) using RANO criteria. Participants without efficacy evalaluation data or survival data censored at day 1. Participants without measurable disease will not be included.

  Up to 2 years after beginning treatment

• Duration of response

  Time from first RANO response to disease progression in participants who achieve a PR or better.

  Up to 2 years after beginning treatment

• Number of participants with treatment-emergent adverse events

  Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of durvalumab. AEs are considered to be treatment emergent if they occur or worsen in severity after the first dose of study treatment.

  Up to 3 months after beginning therapy

Secondary Outcomes (1)

• Overall survival

  Up to 2 years after beginning treatment

Study Arms (2)

Cohort 1

EXPERIMENTAL

Patients with bevacizumab-refractory recurrent glioma with PTEN or TERT gene mutations,determined according to the dynamics of TISF (Tumor in Situ Fluid) ctDNA.

Drug: Tislelizumab plus Bevacizumab

Cohort 2

EXPERIMENTAL

Patients with bevacizumab-refractory recurrent glioma without PTEN or TERT gene mutations,determined according to the dynamics of TISF (Tumor in Situ Fluid) ctDNA.

Drug: Tislelizumab plus Bevacizumab

Interventions

Tislelizumab plus Bevacizumab DRUG

200mg Tislelizumab plus 3mg/kg bevacizumab every 3 weeks

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of thestudy, including disease assessment by MRI and tumor in situ fluid (TISF) collection
• Histologically confirmed diagnosis of glioma
• Resection surgery done at the study center (Henan Provincial People'sHospital), with an reservoir intraoperatively implanted connecting the surgical cavity and the subscalp for postoperative noninvasive TISF collection
• An interval of \> 28 days and full recovery (i.e., no ongoing safety issues) from surgical resection prior to grouping
• Karnofsky performance status (KPS) of 70 or higher
• Life expectancy \> 12 weeks

You may not qualify if:

• More than two recurrences of GBM
• Presence of extracranial metastatic, significant leptomeningeal disease or tumors primarily localized to the brainstem or spinal cord
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring chronic and systemic immunosuppressive treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects have any other condition requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days. Inhaled or topical steroids and adrenal replacement doses \>10mg daily prednisone equivalent are permitted in absence of active autoimmune disease
• Previous radiation therapy with anything other than standard radiation therapy (i.e., focally directed radiation) administered as first line therapy
• Previous treatment with carmustine wafer except when administered as first line treatment and at least 6 months prior to randomization
• Previous bevacizumab or other VEGF or anti-angiogenic treatment
• Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy
• Evidence of \> Grade 1 CNS hemorrhage on the baseline MRI scan
• Inadequately controlled hypertension (defined as systolic blood pressure ≥160 mmHg and /or diastolic blood pressure ≥100 mmHg) within 7 days of first study treatment
• Prior history of hypertensive crisis, hypertensive encephalopathy, reversible posterior leukoencephalopathy syndrome (RPLS)
• Prior history of gastrointestinal diverticulitis, perforation, or abscess
• Clinically significant (i.e., active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start of study treatment
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month prior to randomization

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead

Study Sites (1)

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

Location

Related Publications (1)

• Guo G, Zhang Z, Zhang J, Wang D, Xu S, Liu G, Gao Y, Mei J, Yan Z, Zhao R, Wang M, Li T, Bu X. Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis. Cancer Immunol Immunother. 2024 Aug 6;73(10):193. doi: 10.1007/s00262-024-03774-7.

  PMID: 39105794 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

tislelizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xingyao Bu, MD, PhD

  Henan Provincial People's Hospita

  STUDY DIRECTOR

Central Study Contacts

Xingyao Bu, MD, PhD

CONTACT

+86037165580295; xingyaob@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2022
• First Posted: September 14, 2022
• Study Start: October 5, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)