临床试验/NCT03307785

NCT03307785已完成1 期

Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer

Tesaro, Inc.1 个研究点分布在 1 个国家目标入组 60 人开始时间: 2017年10月12日最近更新: 2025年11月25日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Tesaro, Inc.
入组人数: 60
试验地点: 1
主要终点: Part C: Number of Participants With DLT

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.

Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.

Part E: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part F: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part G: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part H: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part I: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer as outlined below according to study part and disease type:
•Part A: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
•Part B: Patients with advanced or metastatic cancer for which treatment with carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
•Part C: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
•Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
•Part E and F: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) Non-Squamous NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
•Part G, H, and I: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
•Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•Patient has adequate organ function.
•Female patient has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential.
•Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
•Patient has measurable lesions by RECIST v1.
•For Part A and C, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:
•Patient is able to take oral medications.
•For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is necessary.

排除标准

•(Patients will not be eligible for the study entry if any of the following criteria are met)
•Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
•Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
•Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy.
•Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation
•Patient is pregnant or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
•Note: No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from niraparib, female patients should not breastfeed during treatment with niraparib and for 1 month after receiving the final dose.
•Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
•Patient has known active hepatitis B or hepatitis C.
•Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
•Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
•Patient has undergone prior treatment with a known PARP inhibitor.
•Known history or current diagnosis of MDS or AML.
•Patient has a known hypersensitivity to TSR-042 components or excipients.
•For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of the following additional exclusion criterion are met:
•Patient has a known hypersensitivity to any of the following relevant study treatments: carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients.
•For Parts C and D only, patients will not be eligible for study entry if the following additional exclusion criterion is met:
•Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment.
•Patient has a history of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
•Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
•Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
•Patient has a known hypersensitivity to bevacizumab components or excipients.
•For Parts E and F only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
•Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting agents, such as piroxicam.
•Patient is unable or unwilling to take folic acid, vitamin B12 supplement.
•Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
•For Parts G, H, and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
•Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
•For Parts E, F, G, H and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
•Patient has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

研究组 & 干预措施

Part A: TSR-042 and niraparib 200 mg QD

Experimental

Patients will receive TSR-042 500 milligram (mg), intravenous (IV) infusion on Day 1 of every cycle (every 3 weeks [Q3W]) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (every 6 weeks [Q6W]) beginning on Day 1 of Cycle 5 along with niraparib 200 mg, once daily (QD), orally on Days 1 to 21 repeated Q3W.

干预措施: Niraparib (Drug)

Part A: TSR-042 and niraparib 200 mg QD

Experimental

干预措施: TSR-042 (Drug)

Part A: TSR-042 and niraparib 300 mg QD

Experimental

干预措施: Niraparib (Drug)

Part A: TSR-042 and niraparib 300 mg QD

Experimental

干预措施: TSR-042 (Drug)

Part B: TSR-042 and carboplatin-paclitaxel

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 milligram per square meter (mg/m^2), IV infusion on Day 1 Q3W administered for 4 to 6 cycles.

干预措施: TSR-042 (Drug)

Part B: TSR-042 and carboplatin-paclitaxel

Experimental

干预措施: Carboplatin-Paclitaxel (Drug)

Part C: TSR-042, niraparib 200 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Niraparib (Drug)

Part C: TSR-042, niraparib 200 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: TSR-042 (Drug)

Part C: TSR-042, niraparib 200 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Bevacizumab (Drug)

Part C: TSR-042, niraparib 300 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Niraparib (Drug)

Part C: TSR-042, niraparib 300 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: TSR-042 (Drug)

Part C: TSR-042, niraparib 300 mg QD and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Bevacizumab (Drug)

Part D: TSR-042, carboplatin-paclitaxel and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: TSR-042 (Drug)

Part D: TSR-042, carboplatin-paclitaxel and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Carboplatin-Paclitaxel (Drug)

Part D: TSR-042, carboplatin-paclitaxel and bevacizumab

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.

干预措施: Bevacizumab (Drug)

Part E: TSR-042 and carboplatin-pemetrexed

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation) administered for 6 cycles (each cycle is 21 days).

干预措施: TSR-042 (Drug)

Part E: TSR-042 and carboplatin-pemetrexed

Experimental

干预措施: Carboplatin-Pemetrexed (Drug)

Part F: TSR-042, TSR-022, and carboplatin-pemetrexed

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); and TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W administered for 5 cycles (each cycle is 21 days); and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation).

干预措施: TSR-042 (Drug)

Part F: TSR-042, TSR-022, and carboplatin-pemetrexed

Experimental

干预措施: TSR-022 (Drug)

Part F: TSR-042, TSR-022, and carboplatin-pemetrexed

Experimental

干预措施: Carboplatin-Pemetrexed (Drug)

Part G: TSR-042 and carboplatin-nab-paclitaxel

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (every week [Q1W]) of every 3 week cycle for 4 to 6 cycles.

干预措施: TSR-042 (Drug)

Part G: TSR-042 and carboplatin-nab-paclitaxel

Experimental

干预措施: Carboplatin-Nab-Paclitaxel (Drug)

Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxel

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (Q1W) of every 3 week cycle for 4 to 6 cycles.

干预措施: TSR-042 (Drug)

Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxel

Experimental

干预措施: TSR-022 (Drug)

Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxel

Experimental

干预措施: Carboplatin-Nab-Paclitaxel (Drug)

Part I: TSR-042, TSR-022, and carboplatin-paclitaxel

Experimental

Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days).

干预措施: TSR-042 (Drug)

Part I: TSR-042, TSR-022, and carboplatin-paclitaxel

Experimental

干预措施: Carboplatin-Paclitaxel (Drug)

Part I: TSR-042, TSR-022, and carboplatin-paclitaxel

Experimental

干预措施: TSR-022 (Drug)

结局指标

主要结局

Part C: Number of Participants With DLT

时间窗: 21 days

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for \>=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for \>=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for \>=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (\>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

Part A: Number of Participants With Dose-limiting Toxicity (DLT)

时间窗: 21 days

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for \>=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for \>=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for \>=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (\>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D).

Part B: Number of Participants With DLT

时间窗: 21 days

Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 28.5 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

Part D: Number of Participants With DLT

时间窗: 21 days

Part G: Number of Participants With DLT

时间窗: 21 days

Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 22.5 months

Part F: Number of Participants With DLT

时间窗: 21 days

Part H: Number of Participants With DLT

时间窗: 21 days

Part E: Number of Participants With DLT

时间窗: 21 days

Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 9.5 months

Part H: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 24 months

Part I: Number of Participants With DLT

时间窗: 21 days

Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)

时间窗: Up to 28.5 months

Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 4.4 months

Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 3.5 months

Part G: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 24 months

Part I: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

时间窗: Up to 24 months

次要结局

Part A: Objective Response Rate(Up to 28.5 months)
Part D: Objective Response Rate(Up to 9.5 months)
Part E: Objective Response Rate(Up to 4.4 months)
Part B: Objective Response Rate(Up to 28.5 months)
Part I: Objective Response Rate(Up to 24 months)
Part F: Disease Control Rate(Up to 3.5 months)
Part I: Disease Control Rate(Up to 24 months)
Part C: Objective Response Rate(Up to 22.5 months)
Part F: Objective Response Rate(Up to 3.5 months)
Part C: Duration of Response(Up to approximately 60 months)
Part E: Duration of Response(Up to 4.4 months)
Part A: Progression-free Survival(Up to 28.5 months)
Part I: Progression-free Survival(Up to 24 months)
Part G: Objective Response Rate(Up to 24 months)
Part H: Objective Response Rate(Up to 24 months)
Part A: Duration of Response(Up to 28.5 months)
Part B: Duration of Response(Up to approximately 66 months)
Part D: Duration of Response(Up to approximately 62.5 months)
Part F: Duration of Response(Up to 3.5 months)
Part H: Duration of Response(Up to 24 months)
Part I: Duration of Response(Up to 24 months)
Part C: Disease Control Rate(Up to 22.5 months)
Part D: Progression-free Survival(Up to 9.5 months)
Part A: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 28.5 months)
Part E: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 4.4 months)
Part F: Number of Participants With Positive Anti-TSR-022 Antibodies(Up to 3.5 months)
Part G: Duration of Response(Up to 24 months)
Part A: Disease Control Rate(Up to 28.5 months)
Part B: Disease Control Rate(Up to 28.5 months)
Part D: Disease Control Rate(Up to 9.5 months)
Part E: Disease Control Rate(Up to 4.4 months)
Part C: Progression-free Survival(Up to 22.5 months)
Part B: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 28.5 months)
Part I: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 24 months)
Part G: Disease Control Rate(Up to 24 months)
Part H: Disease Control Rate(Up to 24 months)
Part B: Progression-free Survival(Up to 28.5 months)
Part E: Progression-free Survival(Up to 4.4 months)
Part F: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 3.5 months)
Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part F: Progression-free Survival(Up to 3.5 months)
Part G: Progression-free Survival(Up to 24 months)
Part H: Progression-free Survival(Up to 24 months)
Part C: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 22.5 months)
Part D: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 9.5 months)
Part G: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 24 months)
Part B: AUC0-t of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: AUC0-t of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: AUC0-t of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: AUC0-t of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Number of Participants With Positive Anti-TSR-042 Antibodies(Up to 24 months)
Part C: AUC0-t of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: AUC0-t of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part G: AUC0-t of TSR-042(Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part H: Number of Participants With Positive Anti-TSR-022 Antibodies(Up to 24 months)
Part A: AUC(0-t) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part D: AUC0-t of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: AUC0-t of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part A: AUC(0-infinity) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part B: AUC(0-infinity) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part D: AUC(0-infinity) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part G: AUC(0-infinity) of TSR-042(Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part C: Ctau of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part D: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part I: Number of Participants With Positive Anti-TSR-022 Antibodies(Up to 24 months)
Part F: AUC0-t of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: AUC0-t of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: AUC0-t of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: AUC(0-infinity) of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: AUC(0-infinity) of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part E: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: AUC(0-infinity) of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: AUC(0-infinity) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: AUC(0-infinity) of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part F: AUC(0-infinity) of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part B: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part A: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part D: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part F: AUC(0-infinity) of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part H: AUC(0-infinity) of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: AUC(0-infinity) of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part H: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part H: Ctau of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part I: Ctau of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part A: Maximum Observed Plasma (Cmax) of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part F: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Ctau of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part G: Ctau of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Cmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part B: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part C: Cmax of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part F: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Clearance After Intravenous Administration (CL) of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part H: CL of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part E: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Cmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part G: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part I: Cmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part A: Clearance After Oral Administration (CL/F) of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part B: CL of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: CL/F of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part D: CL of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: CL of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part F: CL of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: CL of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part B: Vz of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: Vz/F of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part I: Cmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part C: CL of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part H: Vz of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Vz of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: AUCss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: AUCss of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part I: AUCss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Ctau at Steady State (Ctau,ss) of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part F: CL of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: CL of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: CL of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib(Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part G: Vz of TSR-042(Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part H: Vz of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part G: CL of TSR-042(Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: Vz of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: Vz of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Vz of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part D: Vz of TSR-042(Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part B: AUCss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part D: AUCss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part B: Ctau,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: Ctau,ss of TSR-042(Cycle 2: Pre-dose (each cycle was 21 days))
Part A: Cmax at Steady State (Cmax,ss) of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part D: Cmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part H: Cmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part C: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part D: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part E: Vz of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days))
Part F: Vz of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part C: AUCss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part A: AUC at Steady State (AUCss) of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part F: AUCss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part G: AUCss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: AUCss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part D: Ctau,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: Ctau,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Ctau,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Ctau,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Ctau,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Ctau,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part E: AUCss of TSR-042(Cycle 2: Pre-dose (each cycle was 21 days))
Part F: AUCss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: AUCss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: AUCss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Ctau,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part I: Ctau,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part C: Cmax,ss of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part C: Cmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: Cmax,ss of TSR-042(Cycle 2: Pre-dose (each cycle was 21 days))
Part F: Cmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part C: Ctau,ss of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part C: Ctau,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part G: Ctau,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Cmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: Cmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part A: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part C: Tmax of Niraparib(Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days))
Part B: Cmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part G: Cmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Cmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Cmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Cmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part B: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days))
Part H: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part H: Tmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part I: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part A: Tmax at Steady State (Tmax,ss) of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part A: Tmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: Tmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: Tmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part E: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part G: Tmax of TSR-042(Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part D: Tmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part G: Tmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Vss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part G: Vss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part F: Tmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Tmax of TSR-022(Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days))
Part C: Tmax,ss of Niraparib(Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days))
Part E: Tmax,ss of TSR-042(Cycle 2: Pre-dose (each cycle was 21 days))
Part F: Tmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part B: Tmax,ss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part H: Tmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Tmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Tmax,ss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part D: Vss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part F: Vss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Vss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Tmax,ss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part B: Vss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part C: Vss of TSR-042(Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days))
Part E: Vss of TSR-042(Cycle 2: Pre-dose (each cycle was 21 days))
Part H: Vss of TSR-042(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part H: Vss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days))
Part I: Vss of TSR-022(Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days))

研究者

发起方

Tesaro, Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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