MC# 17-16 - A Phase Ib Study to Assess the Safety, Tolerability, and Clinical Activity of BGB-290 in Combination with Temozolomide (TMZ) in Subjects with Locally Advanced or Metastatic Solid Tumors
Agent(s): BGB-290, Temozolomide (TMZ)
Disease Type(s): Esophageal, Head and Neck, Sarcoma, Lung-NSCLC
Phase(s): I, II
Drug Classification(s): Targeted Therapy, Small Molecule
Molecular Target(s): BRCA, PARP
Mechanism of Action
BGB-290 is a highly potent and selective inhibitor of PARP1 and PARP2
In this study, the sponsor and investigators want to learn:
- How much BGB-290 and TMZ can be given with an acceptable level of side effects
- The effects of BGB-290 and TMZ when given in combination
- How much BGB-290 and how much of TMZ is absorbed into the blood and how fast it is removed
- Subject has voluntarily agreed to participate by signing an informed consent
- Male or female and ≥18 years of age on day of signing an informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- Ability to swallow whole capsules
- Subjects who have histologically or cytologically confirmed malignancy that has progressed to the advanced or metastatic stage
- If available, agreement to provide archival tumor tissue for exploratory biomarker analyses
- NOTE: If archival tumor tissue is not available, an optional fresh biopsy if highly recommended.
- Subject must have adequate organ function as indicated by the following screening laboratory values (obtained ≤2 weeks prior to Day 1):
- Absolute neutrophil count (ANC) ≥1.5×109/L
- Platelets ≥ 100×109/L
- Hemoglobin ≥ 9 g/dL or ≥5.6 mmol/L (Note: Criteria must be met without a transfusion within 2 weeks of obtaining the sample)
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN) or estimated creatinine clearance ≥ 50 mL/min (calculated using the institutional standard method)
- Total serum bilirubin ≤ 1.5 X ULN (total bilirubin must be < 4 X ULN for subject with Gilbert’s syndrome)
- Aspartate and alanine aminotransferase (AST and ALT, respectively) ≤ 3 x ULN OR ≤ 5 X ULN for subject with liver metastases
- Serum albumin ≥ 3 g/dL
- Females of childbearing potential and non-sterile males must agree to practice highly effective methods of birth control for the duration of the study and for≥ 3 months after the last dose of study drug.
- Willingness and ability to comply with all protocol-specified requirements
- Known hypersensitivity to any temozolomide (TMZ) component or to dacarbazine (DTIC)
- Prior treatment with a PARP inhibitor (except for iniparib)
- Received chemotherapy, biologic therapy, immunotherapy, or investigational agent within 3 weeks (or ≤ 5 half-lives, whichever is shorter) (unless otherwise noted in the Inclusion Criteria) prior to Day 1
- Subjects who are considered to be refractory to platinum-based therapy (e.g., progressive disease at the first tumor assessment while receiving platinum treatment) (for subjects in Dose Escalation Phase only)
- Have any unresolved acute effects of any prior therapy of Grade 2 or higher, except for AEs not constituting a safety risk by investigator judgment
- Had a major surgical procedure, open biopsy, or significant traumatic injury ≤ 4 weeks prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
- Placement of vascular access device is not considered major surgery.
- Have other diagnosis of malignancy
- Except for surgically excised non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, localized prostate cancer treated with curative intent, adequately treated low-stage bladder cancer, ductal carcinoma in situ treated surgically with curative intent, or a malignancy diagnosed >2 years ago, with no current evidence of disease and no therapy ≤ 2 years prior to Day 1.
- Subject who has received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy before recording baseline symptoms.
- Have untreated leptomeningeal or brain metastasis. Subject with previously treated brain metastases is eligible if the metastases have shown no progression on brain computed tomography (CT) or magnetic resonance imaging (MRI) over at least 4 weeks, the subject has no symptoms due to the brain metastases, and the subject has been off corticosteroids for ≥2 weeks.
- Have active infection requiring systemic treatment
- Have known human immunodeficiency virus (HIV) infection or active viral hepatitis
- Have any of the following cardiovascular criteria:
- Current evidence of cardiac ischemia
- Current symptomatic pulmonary embolism
- Acute myocardial infarction ≤6 months prior to Day 1
- Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to Day 1
- Grade ≥2 ventricular arrhythmia ≤6 months prior to Day 1
- Cerebral vascular accident (CVA) ≤6 months prior to Day 1
- Have an active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or had previous complete gastric resection or lap-band surgery
- Gastroesophageal reflux disease under treatment with proton-pump inhibitors is allowed (assuming no drug interaction potential).
- Use or have anticipated need for food or drugs known to be strong or moderate cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers ≤10 days (or ≤5 half-lives, whichever is shorter) prior to Day 1
- Are pregnant or nursing (Females of childbearing potential require a negative serum pregnancy test ≤7 days before Day 1)
- Dallas, TX - Mary Crowley Cancer Research - Medical City