A Phase II Study of Talazoparib (BMN 673) in Patients With Homologous Recombination Repair Deficiency Positive Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1,152
- 主要终点
- Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants
研究概览
简要总结
This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the overall response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib (BMN 673) in HRRD Medivation (MDVN)-positive patients.
SECONDARY OBJECTIVES:
I. To evaluate investigator assessed progression-free survival (IA-PFS) and overall survival (OS) associated with therapy in HRRD MDVN-positive patients.
II. To evaluate ORR, IA-PFS, and OS in HRRD Foundation Medicine, Inc. (FMI)-positive patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
- •Patients must be assigned to S1400G; S1400G biomarker eligibility defined as homologous recombination repair deficiency (HRRD) positive is as follows
- •Biomarker-positive group
- •HRRD by FMI
- •Homologous recombination repair deficiency by Foundation Medicine Inc., criteria
- •Alteration type
- •Truncating mutation, frameshift deletions, indels missense and nonsense mutations predicted to have functional consequence in any of the specified genes
- •Eligible alteration
- •Mutation in any one of the following critical HRR pathway genes: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1
- •Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib [BMN 673]) as its primary pharmacology
- •Patients must have achieved stable disease, a partial response, or a complete response at their first disease assessment after initiating first-line platinum-based chemotherapy; patients determined to have progressed (in the opinion of the treating physician) at their first disease assessment are not eligible
- •Patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of talazoparib (BMN 673) (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or active peptic ulcer disease); patients must not have active small or large intestine inflammation such as Crohn's disease or ulcerative colitis (within 12 months of sub-study registration)
- •Patients must be able to take oral medications; patients must be able to swallow capsules whole without crushing or altering them in any way
- •Patients must not be taking, nor plan to take while on protocol treatment strong P-glycoprotein (P-gp) inhibitors, P-gp inducers, or breast cancer resistance protein (BCRP) inhibitors; the language ?P-gp or BCRP inhibitors or inducers? is reworded to ?strong P-gp inhibitors, P-gp inducers, or BCRP inhibitors? for consistency with the investigator brochure
- •Patients must agree to have blood specimens submitted for pharmacokinetic analysis
排除标准
- 未提供
研究组 & 干预措施
Treatment (talazoparib)
Patients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (talazoparib)
Patients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (talazoparib)
Patients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Talazoparib (Drug)
结局指标
主要结局
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants
时间窗: Up to 3 years post sub-study registration
The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). With 40 HRRD subset positive patients, overall response rate can be estimated within 13% with 95% confidence.
次要结局
- Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants(3 years post sub-study registration)
- Duration of Response in HRRD-positive (FMI) Participants(Up to 3 years)
- Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants(Up to 3 years post sub-study registration)
- Overall Survival (OS) in HRRD-positive (MDVN) Participants(Up to 3 years post sub-study registration)
- Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Duration of treatment and follow up until death or 3 years post registration)
- Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants(3 years post sub-study registration)
- Overall Survival (OS) in HRRD-positive (FMI) Participants(3 years post sub-study registration)
- Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-negative Per MDVN But HRRD-positive Per FMI Participants(3 years post sub-study registration)