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Monoclonal Antibodies

AB154 + AB122 for Glioblastoma

Phase < 1

Recruiting

Led By Sylvia Kurz, MD

Research Sponsored by Yale University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have adequate organ and marrow function as defined below within 14 days of treatment: Absolute neutrophil count (ANC) ≥1,500 /mcL, Platelets ≥100,000 / mcL, Hemoglobin ≥9 g/dL or ≥ 5.6 mmol/L without transfusion or Erythropoietin (EPO) dependency (within 7 days of assessment), Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN, Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN, aspartate aminotransferase and alanine transaminase (SGPT) ≤ 2.5 X ULN, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, An interval of >=12 weeks from the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiation treatment field, An interval of >=3 weeks or 5 half-lives (whichever is longer) after the last administration of any investigational agent or any other treatment prior to first study dose, Female subjects of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

- Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

Must not have

Has an active infection requiring systemic therapy.

Has a known history of active tuberculosis (Bacillus Tuberculosis).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 2 years

Summary

This trial is testing a new combination of drugs to treat glioblastoma, a type of brain cancer. The trial is divided into two groups, with the first group receiving the new combination of drugs to test for safety and the second group receiving the new combination of drugs as well as surgery.

Who is the study for?

Adults with first or second recurrence of glioblastoma, who've had radiation therapy and are suitable for tumor removal surgery. They must have a good performance status (able to carry out daily activities), adequate organ function, and agree to use birth control. Excluded are those on high steroid doses, prior immune checkpoint inhibitor treatment, known immunodeficiency or active hepatitis, other progressing cancers, active autoimmune disease requiring recent treatment, multifocal disease (Cohort B only), current serious infections or conditions that could affect trial participation.

What is being tested?

The study tests AB154 combined with AB122 in patients with recurrent glioblastoma. It has two parts: Cohort A checks safety at specific dosages; Cohort B further evaluates safety and collects tissue/blood samples for research on how the drugs work within tumors. Participants will receive intravenous treatments of both drugs.

What are the potential side effects?

Specific side effects aren't listed but may include typical reactions to cancer therapies such as fatigue, infusion-related reactions like fever or chills, potential organ inflammation due to immune response modification by the drugs being tested.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is within the normal range.

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I can carry out normal activities with minimal symptoms.

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My cancer has come back once or twice after treatment, which included radiation.

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My diagnosis is Grade IV glioblastoma.

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My hemoglobin level is above 9 g/dL without needing transfusions or EPO.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently being treated for an infection.

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I have an active tuberculosis infection.

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I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

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I need high doses of steroids to manage my condition.

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I have a history of or currently have non-infectious lung inflammation.

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I am currently or have previously been treated with drugs that boost the immune system.

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I have been diagnosed with an immunodeficiency condition, such as HIV/AIDS.

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I have active Hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] associated with the combination AB122 and AB154 in patients with recurrent glioblastoma

Secondary study objectives

Single cell RNA sequencing of tumor and blood after exposure to AB154 with and without AB122

Tregs and CD8 T cells ratio by immunofluorescence

Trial Design

5Treatment groups

Experimental Treatment

Group I: Placebo Surgical Cohort (Cohort B4)Experimental Treatment1 Intervention

Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B4 (N=10): Two placebo infusions Following surgery, all patients will initiate treatment with the combination of AB154 and AB122. AB154 will be given at a dose of 10 mg/kg and AB122 will be given at a dose of 240 mg (flat).

Group II: AB154 Surgical Cohort (Cohort B1)Experimental Treatment2 Interventions

Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B1 (N=10): AB154 single agent (10 mg/kg) + placebo Following surgery, all patients will initiate treatment with the combination of AB154 and AB122. AB154 will be given at a dose of 10 mg/kg and AB122 will be given at a dose of 240 mg (flat).

Group III: AB154 + AB122 Surgical Cohort (Cohort B3)Experimental Treatment2 Interventions

Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B3 (N=10): AB154 (10 mg/kg) +AB122 (240 mg) Following surgery, all patients will initiate treatment with the combination of AB154 and AB122. AB154 will be given at a dose of 10 mg/kg and AB122 will be given at a dose of 240 mg (flat).

Group IV: AB122 Surgical Cohort (Cohort B2)Experimental Treatment2 Interventions

Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B2 (N=10): AB122 single agent (240 mg) + placebo Following surgery, all patients will initiate treatment with the combination of AB154 and AB122. AB154 will be given at a dose of 10 mg/kg and AB122 will be given at a dose of 240 mg (flat).

Group V: AB122 + AB154 Safety Cohort (Cohort A)Experimental Treatment2 Interventions

Eligible patients will be sequentially enrolled to receive intravenous AB154 combined with AB122 (N=6). AB154 will be given at a dose of 10 mg/kg and AB122 will be given at a dose of 240 mg (flat).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

0 / 15Eligibility criteria met