A Phase II, Multi-center, Single-arm, Open-label Study to Assess the Efficacy and Safety of Tenalisib, a PI3K δ/γ, and SIK3 Inhibitor, in Patients with Metastatic Triple Negative Breast Cancer (TNBC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- a. Clinical benefit rate (CBR) defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) for 16 weeks or longer based on Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 on treatment
研究概览
简要总结
The objective of this Phase II, open-label, single-arm, study, is to evaluate the efficacy and safety of tenalisib in 40 patients with metastatic TNBC, who have received at least one but not more than 3 prior therapies in a metastatic setting.
Tenalisib at the dose of 400 mg BID will be administered orally in 28 days of the cycle until disease progression, consent withdrawal, or unacceptable toxicity
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.Female patients who provide informed consent prior to any study-specific procedures.
- •2.Patients must be ≥18 years of age, at the time of signing informed consent.
- •3.Female patients who have histologically confirmed TNBC, defined as having ≤1% cellular expression of ER and PR as determined by immunohistochemistry (IHC), and HER2 expression of 0 to 1+ by IHC, or 2+ by IHC and fluorescence in situ hybridization (FISH) negative, according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines.
- •4.Patients who have received at least 1 but not more than 3 prior chemotherapy regimens in a metastatic setting.
- •5.Patients with at least one measurable lesion, per RECIST version 1.1 at baseline (i.e., lesion ≥10 mm in the longest diameter; lymph nodes ≥15 mm in short axis) that can be accurately assessed by CT scan or MRI and is suitable for repeated assessment at follow-up visits.
- •Bone-only disease is not permitted.
- •6.ECOG performance status 0 to
- •7.Life expectancy of at least 3 months.
- •8.Adequate bone marrow, liver, and renal functions as assessed within 7 (±2) days before the first dose of the study drug as defined below: a.
- •Hemoglobin ≥ 9.0 g/dL (shouldn’t be transfused or treated with erythropoietin to maintain or exceed this level).
- •Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor support.
- •Platelet count ≥ 150 x 109/L.
- •ALT and AST ≤ 3 x ULN (≤ 5 x ULN for patients with liver metastasis or liver involvement).
- •Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula) for patients with creatinine levels above ULN.
- •9.Female patients of childbearing potential should be willing to use a medically acceptable method of contraception while participating in the study and for 30 days after the last dose of the study drug AND must have a negative serum pregnancy test within 72 hours prior to Cycle 1 Day 1 (C1D1).
- •10.Ability to swallow and retain oral medication.
- •11.Willingness and capability to comply with the study requirements.
排除标准
- •1.Patients receiving anticancer therapy (e.g., chemotherapy, biologic therapy, or any other investigational product) within 4 weeks or 5 half-lives of the drug prior to C1D1, whichever is shorter.
- •2.Patient who has not recovered from acute toxicities (defined as NCI-CTCAE grade > 1) of previous therapy except treatment-related alopecia.
- •(Note: Patients with any unresolved toxicities which in the opinion of PI are stable and controlled with medication can be enrolled in the study).
- •3.Prior exposure to PI3K inhibitors (e.g., alpelisib, buparlisib) for breast cancer.
- •4.Major surgery within 4 weeks of starting study treatment OR any patient who has not recovered from the effects of major surgery.
- •5.Patient with symptomatic uncontrolled brain metastasis.
- •(Note: A scan to confirm the absence of brain metastases is not required.
- •Patients whose brain metastatic disease has remained stable for ≥ 4 weeks (prior to the start of study treatment) following treatment of brain metastases are eligible.
- •The patient can receive a stable dose of corticosteroids before and during the study if steroids were started at least 4 weeks prior to C1D1).
- •HIV-positive patients who are on antiretroviral therapy OR active hepatitis C OR active hepatitis B virus infections.
- •(Note: Documentation of infection HIV, HBV, and HCV will be done based on medical history).
- •7.Ongoing immunosuppressive therapy including systemic corticosteroids except as allowed per concomitant medication.
- •8.Known history of severe liver injury (e.g., alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension) as judged by the investigator.
- •(Note: Exception will be patients with liver metastasis who can be enrolled in the study).
- •9.History of severe cutaneous reactions [e.g., Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), or Toxic Epidermal Necrolysis (TEN)] in the past.
- •10.Active gastrointestinal tract disease with malabsorption syndrome or uncontrolled inflammatory gastrointestinal diseases such as Crohn’s disease or ulcerative colitis, as judged by the investigator.
- •11.Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication or clinically relevant findings in the ECG such as second-or third-degree AV block, significant prolongation of the QTcF interval, unless agreed between the investigator and the medical monitor.
- •12.Concurrent disease or condition that would interfere with study participation or safety, such as the following: a.
- •Active, clinically significant infection requiring a parenteral antimicrobial agent.
- •Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorder.
- •Mood disorders like OCD, severe depression, history of suicidal attempts, schizophrenia, etc.
- •as per the investigator’s discretion 13.Concurrent medications or substances with the potential to affect the activity or pharmacokinetics of tenalisib, as reviewed and confirmed by a medical monitor.
- •Pregnancy or lactation.
- •15.Patients with other active malignancies at the time of screening except for adequately treated in situ carcinoma of the cervix uteri or basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.
- •(Note: Patients with prior malignancies which are treated and are in remission without requiring active treatment are allowed in the study.)
- •A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive study treatment or whose control may be jeopardized by the complications of this therapy.
结局指标
主要结局
a. Clinical benefit rate (CBR) defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) for 16 weeks or longer based on Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 on treatment
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
Efficacy-
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
b. Duration of Clinical Benefit (DoCB).
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
c. Overall Response Rate (ORR), & Duration of Response (DoR).
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
d. Progression Free Survival (PFS).
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
Safety- To evaluate & grade Adverse Events (AEs), grade 3/4 AEs, & Serious Adverse Events (SAEs), using NCI-CTCAE Version 5.0.
时间窗: Radiological assessment by RECIST version 1.1 at C3D1 (± 7 days) & approximately 8 weeks thereafter (± 7 days), and/ or at the EOT, & as clinically indicated (if clinical progression is suspected).
次要结局
- Pharmacokinetics-Trough plasma concentrations of tenalisib & its metabolite (IN0385).(Exploratory- Correlation of efficacy to baseline mutational status (PIK3CA, AKT1, PTEN, TP53, INPP4B, BRCA1, and BRCA2).)