Beigene clinical trial at UCSF

A Study Assessing BGB-290 With Radiation and/or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma

 

Summary

This clinical trial will evaluate the safety, efficacy and clinical activity of BGB-290 in combination with radiation therapy and/or temozolomide (TMZ), for treating patients with newly diagnosed or recurrent glioblastoma.

BGB-290 is a drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. More specifically, it inhibits PARP proteins that are required for DNA repair, potentially making cancer cells more susceptible to DNA-damaging chemotherapy drugs. This clinical trial will test how well the combination of BGB-290 with radiation therapy and/or TMZ works in treating patients with glioblastoma.

Eligible participants will be assigned to treatment groups based on their tumor status (newly diagnosed vs recurrent) and based on genetic features of the tumor (whether the MGMT gene is unmethylated):

  • Arm A (newly diagnosed, MGMT unmethylated): BGB-290 with radiation therapy
  • Arm B (newly diagnosed, MGMT unmethylated): BGB-290 with radiation therapy + TMZ
  • Arm C (recurrent): BGB-290 + TMZ

 

Inclusion Criteria
  1. Age ≥ 18 years old.
  2. Confirmed diagnosis of glioblastoma (WHO Grade IV).
  3. Ability to undergo serial MRIs.
  4. ECOG status ≤ 1.
  5. Adequate bone marrow function.
  6. Adequate renal and hepatic function.
  7. Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 90 days after last dosing.
  8. Ability to swallow whole capsules.

Subjects in Arms A and B (not Arm C) must also meet inclusion criteria below:

  1. No previous treatment for GB except surgery.
  2. Able to start radiation therapy ≤ 49 days after surgery but ≥ 14 days after a biopsy or ≥28 days after an open biopsy or craniotomy with adequate wound healing.
  3. Documented unmethylated MGMT promoter status.

Subjects in Arm C must also meet inclusion criteria below:

  1. No prior systemic chemotherapy other than TMZ for GB.
  2. Progressive disease > 2 months after completion of first line therapy.
  3. At least one measurable lesion by mRANO.

Subjects in Arm C Phase 2, Cohort C1 must also meet criteria below. This is not applicable to subjects enrolled in Arm C, Ph 1b.

  1. Documentation of unmethylated MGMT promoter status.

Subjects in Arm C Phase 2, Cohort C2 must also meet criteria below. This is not applicable to subjects enrolled in Arm C Phase 1b.

  1. Documentation of methylated MGMT promoter status.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.
  2. Toxicity of ≥ Grade 2 from prior therapy.
  3. Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.
  4. History of other active malignancies within 2 years with exception of (i) adequately treated in situ cancer of the cervix, (ii) non-melanoma skin cancer, or (iii) localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment ≤ 2 years prior to study treatment.
  5. Uncontrolled seizure disorder.
  6. Active infection requiring systemic treatment.
  7. Known human immunodeficiency virus (HIV) or active viral hepatitis.
  8. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment.
  9. Active clinically significant gastrointestinal disease.
  10. Active bleeding disorder ≤ 6 months prior to start of treatment.
  11. Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
  12. Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
  13. Pregnant or nursing females.
  14. Significant intercurrent illness that may result in subject's death prior to death from glioblastoma.
  15. Known hypersensitivity to any component of TMZ or decarbazine (DTIC). [Subjects in Arms B and C only.]

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

Investigator(s)

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