Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors

Status: Active

Description

This study is to evaluate the safety, efficacy and clinical activity of BGB-290 and temozolomide (TMZ) in subjects with locally advanced or metastatic solid tumors.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: All subjects 1. Age ≥18 years old. 2. Confirmed malignancy at advanced or metastatic stage. 3. ECOG status ≤ 1. 4. Adequate bone marrow function. 5. Adequate renal and hepatic function. 6. 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. 7. Must have measurable or evaluable disease per RECIST [Dose escalation phase only] Additional inclusion criteria 8 - 12 are specific to tumor types in dose expansion phase: 8. Ovarian cancer 1. Previously received at least 1 line of platinum containing chemotherapy. 2. No progression or recurrent disease in 6 months from last platinum containing regimen. 9. Triple-Negative Breast Cancer a. 0 - 1 prior platinum-containing regimen (any treatment setting) and received ≤ 3 prior regimens (advanced or metastatic setting). 10. Prostate cancer 1. Documented progressive disease. 2. Chemotherapy-naïve or previously received ≤2 taxane-based regimens. 3. May be pre-or post-treatment with a novel androgen receptor targeted agent. 4. Completed in ≥ 2 weeks radiation or treatment with anti-androgen agents. 11. Ovarian, breast and prostate cancer: If homologous recombinant deficiency (HRD) or BRCA status unknown, need pre-screening for eligibility. 12. Small cell lung and gastric cancer: previously received ≤ 2 prior lines of therapy. Exclusion Criteria: All subjects 1. Prior exposure to a PARP inhibitor. 2. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents within 3 weeks prior to start of study treatment. 3. Refractory to platinum-based therapy. 4. Toxicity of ≥ Grade 2 from prior therapy. 5. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment. 6. History of other active malignancies within 2 years with exception of (i) adequately treated in situ carcinoma 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. 7. Untreated leptomeningeal or brain metastasis. 8. Active infection requiring systemic treatment. 9. Known human immunodeficiency virus (HIV) or active viral hepatitis. 10. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment. 11. Active, clinically significant gastrointestinal disease. 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.

Locations & Contacts

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New York

Bronx
Montefiore Medical Center-Einstein Campus
Status: Approved
Name Not Available
Montefiore Medical Center-Weiler Hospital
Status: Active
Name Not Available
New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

This is an open-label study of BGB‑290 and temozolomide (TMZ) with a dose escalation and dose expansion phase. Dose escalation will evaluate safety, tolerability, preliminary efficacy, and PK and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) for the two drug combination. It is a modified 3+3 dose escalation scheme with a fixed dose of BGB‑290 in combination with escalating doses of TMZ. Dose expansion will evaluate the safety, PK profile and anti-tumor activity of BGB-290 and TMZ at a dose/schedule selected from the dose escalation phase. Five different solid malignancy types (n=100) will be evaluated.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
BeiGene USA, Inc.

Trial IDs

Primary ID BGB-290-103
Secondary IDs NCI-2018-00609
Clinicaltrials.gov ID NCT03150810