Neoadjuvant PD-1 Antibody Alone or Combined With DC Vaccines for Recurrent Glioblastoma

Neoadjuvant PD-1 Antibody Alone or Combined With Autologous Glioblastoma Stem-like Cell Antigens-primed DC Vaccines (GSC-DCV) for Patients With Recurrent Glioblastoma：A Phase II, Randomized Controlled, Double Blind Clinical Trial.

Glioblastoma multiforme (GBM) are the most prevalent malignant tumor in central nervous system. At recurrence, no clear standard-of-care therapy is agreed for recurrent GBM (rGBM) and median overall survival is estimated to rarely exceed 6-9 months with effective therapies. Neoadjuvant therapy with anti-PD-1 monoclonal antibodies were confirmed to be helpful to extend survival in rGBM. Vaccine, dendritic cells (DCs) pulsed with glioblastoma stem-like cell (GSC) antigens (GSC-DCV), could extend survival for GBM patients in our previous clinical study (PMID: 30159779). The purpose of this study is to evaluate the safety and efficiency of using the neoadjuvant therapy with PD-1 antibody (Carilizumab) plus DC vaccine (GSC-DCV) in patients with recurrent glioblastoma.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Biological: Camrelizumab plus GSC-DCV; Biological: Camrelizumab plus Placebo

Detailed Description

This is a phase II randomized controlled clinical study. The purpose of this research is to study the safety and efficacy of Camrelizumab alone or combined with GSC-DCV vaccines in treating patients with recurrent glioblastomas. The participants will be randomly assigned into two group. Patients in group A will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression. Patients in group B will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression. Furthermore, to evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events based on the next generation sequencing.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Yao, MD; Phone Number: 86-021-52889999; Email: yu_yao@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital, Fudan University
      • Contact: Yu Yao, MD; Phone Number: 86-021-5288-9999; Email: yu_yao@fudan.edu.cn
      • Principal Investigator: Liangfu Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 18 to 70 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
3. Estimated life expectancy > 3 months.
4. Previous first-line therapy with radiotherapy and chemotherapy, first or second relapse with unequivocal evidence of tumor progression.
5. Pathological diagnosis or molecular diagnosis for lesion this time was confirmed to be recurrent brain glioma (WHO grade 4).
6. Patients with subtotal resection or above of the tumor confirmed with contrast MR within 72 hours after surgery.
7. No high-dose systemic corticosteroids (defined as >10 mg day-1 of prednisone or bio-equivalent for at least seven consecutive days before administration).
8. No antibiotics for at least three consecutive days before administration.

9. Adequate organ function defined by:

   Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0×10^9/L, platelets ≥100×10^9/L; hemoglobin ≥ 8 g/dL. Hepatic: bilirubin 2×upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance >60 ml/min/1.73 m2. Electrocardiogram: normal.

10. Written informed consent.
11. Patient should have good follow-up compliance.

Exclusion Criteria:

1. Pregnant or breast-feeding patients.
2. Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
4. Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
5. Any previous investigational medication within 30 days before first administration of Camrelizumab.
6. History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant PD-1 inhibitor plus DC vaccine; Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression.	Biological: Camrelizumab plus GSC-DCV; Prior to scheduled surgery, patients need to receive Camrelizumab IV (3mg/kg, up to 200mg). After surgery, patients receive Camrelizumab IV (3mg/kg, up to 200mg) and GSC-DCV IH every 3 weeks in the absence of disease progression or unacceptable toxicity.
Active Comparator: Neoadjuvant PD-1 inhibitor plus Placebo; Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression.	Biological: Camrelizumab plus Placebo; Prior to scheduled surgery, patients need to receive Camrelizumab IV (3mg/kg, up to 200mg). After surgery, patients receive Camrelizumab IV (3mg/kg, up to 200mg) and Placebo IH every 3 weeks in the absence of disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from enrollment to the dates of death from any cause or last follow up reported	24 months
Progression-free survival (PFS)	Time from enrollment to the dates of disease progression, death from any cause or last tumor assessment reported between date of first patient enrollment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-related adverse events	Toxicity assessed by Common Terminology Criteria for Adverse Events	12 months
Treatment Responses Rate	Response rate assessed by immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory biomarkers	To investigate the association between biomarkers and clinical outcomes using diverse biospecimen based on the next generation sequencing, including ctDNA, TIL (tumor infiltrating lymphocyte) density and TCR (T cell receptor) Clonality, gene expression signature, genomic mutation, microbial bacteria and so on.	24 months

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.; Shanghai Sunstem Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 28, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Immunotherapy; Glioblastoma; PD-1 antibody; DC vaccine
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: KY2021-547

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No