An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 582
- 试验地点
- 60
- 主要终点
- Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort)
研究概览
简要总结
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.
详细描述
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors. The study has a basket design and includes several cohorts, either defined by an actionable somatic mutation or by actionable mutation and tumor histology, including HER2 mutant breast, HER2 mutant cervical, HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers.
The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 days after the last dose of neratinib and a survival follow-up period.
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
- •Provide written informed consent
- •Histologically confirmed cancers for which no curative therapy exists
- •Documented HER2 or EGFR exon 18 mutation
- •Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol
- •At least one measurable lesion, defined by RECIST v1.1
排除标准
- •Participants harboring ineligible somatic HER2 mutations
- •Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible
- •Participants who are receiving any other anticancer agents
- •Symptomatic or unstable brain metastases
- •Women who are pregnant or breast-feeding
- •There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
研究组 & 干预措施
Neratinib monotherapy
Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations.
Cohorts closed to enrollment in prior amendments: HER2 mutant cancers including bladder/urinary, colorectal, endometrial, breast HR-positive, TNBC HR-negative, lung, gastroesophageal, biliary, and ovarian; HER3 mutant solid tumor NOS; HER4 mutant solid tumor NOS; fibrolamellar carcinoma and EGFR brain.
干预措施: Neratinib (Drug)
Neratinib and Trastuzumab
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers.
Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.
干预措施: Neratinib (Drug)
Neratinib and Trastuzumab
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers.
Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.
干预措施: Trastuzumab (Drug)
Neratinib, Fulvestrant and Trastuzumab (Randomized)
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
干预措施: Neratinib (Drug)
Neratinib, Fulvestrant and Trastuzumab (Randomized)
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
干预措施: Fulvestrant (Drug)
Neratinib, Fulvestrant and Trastuzumab (Randomized)
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
干预措施: Trastuzumab (Drug)
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
干预措施: Neratinib (Drug)
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
干预措施: Fulvestrant (Drug)
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
干预措施: Trastuzumab (Drug)
Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
干预措施: Neratinib (Drug)
Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
干预措施: Paclitaxel (Drug)
Neratinib and Fulvestrant
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
干预措施: Neratinib (Drug)
Neratinib and Fulvestrant
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort)
时间窗: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (cervical cancer cohort). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
时间窗: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts)
时间窗: From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks
Percentage of participants who achieve CR or PR per Response Evaluation Criteria in Sold Tumors Criteria (RECIST) v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts), per RECIST (if assessed) or PERCIST. RECISTv1.1 for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR PERCISTv1.0: Complete Metabolic Response - Complete resolution of 18F-FDG uptake within measurable target lesion so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels Partial Metabolic Response - Reduction of minimum of 30% in target measurable tumour 18F-FDG SULpeak. Absolute drop in SUL must be at least 0.8 SUL units, as well. No new lesions. Positive Metabolic Response - Participants having either "Complete Metabolic Response" or "Part
次要结局
- Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort)(From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months)
- Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)(From first response to first disease progression or death, assessed up to 58 months)
- Duration of Response (DOR) by Investigator Review (All Cohorts)(From first response to first disease progression or death, assessed up to 58 months)
- Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)(From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months)
- Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts)(From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months)
- Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)(From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months)
- Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts)(From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months.)
- Progression-Free Survival (PFS) by Investigator Review (All Cohorts)(From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months)
- Number of Participants With Treatment-Emergent Adverse Events(From first dose through 28 days after the last dose, assessed up to 75 months.)