FRAmework-01: A Three-Part Phase 3 Study of Sofetabart Mipitecan (LY4170156) Versus Chemotherapy or Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer, and Sofetabart Mipitecan Plus Bevacizumab Versus Platinum-Based Chemotherapy Plus Bevacizumab in Platinum-Sensitive Ovarian Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,630
- 试验地点
- 438
- 主要终点
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator
研究概览
简要总结
This is a clinical study that has three parts. It is testing a potential new medicine called Sofetabart Mipitecan (Sofe-M) for people with certain types of ovarian, peritoneal, and fallopian tube cancers. Part A enrolls participants with platinum-resistant cancer, meaning their disease progressed during or within six months of platinum-based chemotherapy. Parts B and C enroll participants with platinum-sensitive cancer, whose disease responded and remained controlled for at least six months after completing platinum treatment. The researchers want to find out if Sofe-M works better than the standard treatments that doctors use now and to better understand how safe it is. Each participant's time in the study will depend on how they respond to the treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Part A, B, and C:
- •Have histologically confirmed high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
- •Have confirmed availability of tumor tissue block or slides
- •Have radiographic progression on or after most recent line of systemic anticancer therapy
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Have measurable disease per RECIST v1.1
- •Have platinum-resistant disease, defined as radiographic progression less than or equal to (≤)6 months of the last administration of platinum therapy.
- •Have previously received 1 to 3 prior lines of systemic cytotoxic therapy. Up to 4 lines of prior cytotoxic therapy is allowed if one of those lines is mirvetuximab soravtansine.
- •Have received prior bevacizumab treatment, unless documented contraindication or intolerance.
- •Have received treatment with a poly (ADP-ribose) polymerase inhibitor (PARPi) if known to have a somatic or germline breast cancer gene (BRCA) mutation, if clinically indicated, unless documented contraindication or intolerance.
- •Part B and C:
- •Have relapsed after first-line platinum-based chemotherapy and have platinum-sensitive disease defined as radiographic progression greater than (>)6 months of their last administration of platinum therapy
- •Have previously received 1 to 2 prior lines of systemic cytotoxic chemotherapy
- •- Have previously received a PARPi, per local product label, with progression on, or within 6 months of completion of PARPi treatment.
- •- Have not previously received a PARPi treatment.
排除标准
- •Parts A, B and C:
- •- Have received prior antibody-drug conjugate (ADC) with a topoisomerase inhibitor payload.
- •Have primary platinum-refractory disease, defined as radiographic progression ≤ 1 month since the last dose of first-line platinum-containing chemotherapy.
- •Part B and C:
- •- Have clinically significant proteinuria
- •- Have a known pathogenic BRCA1/2 gene alteration (somatic or germline).
研究组 & 干预措施
Part C: Sofetabart Mipitecan plus Bevacizumab
Administered IV
干预措施: Sofetabart Mipitecan (Drug)
Part C: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Bevacizumab (Drug)
Part B: LY4170156 plus Bevacizumab
Administered IV.
干预措施: Bevacizumab (Drug)
Part A: Chemotherapy or Mirvetuximab Soravtansine (MIRV)
Investigator's Choice of Chemotherapy or MIRV given IV.
干预措施: Gemcitabine (Drug)
Part A: Chemotherapy or Mirvetuximab Soravtansine (MIRV)
Investigator's Choice of Chemotherapy or MIRV given IV.
干预措施: MIRV (Drug)
Part B: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Bevacizumab (Drug)
Part B: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Gemcitabine (Drug)
Part B: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Carboplatin (Drug)
Part A: Sofetabart Mipitecan
Administered intravenously (IV).
干预措施: Sofetabart Mipitecan (Drug)
Part A: Chemotherapy or Mirvetuximab Soravtansine (MIRV)
Investigator's Choice of Chemotherapy or MIRV given IV.
干预措施: Topotecan (Drug)
Part A: Chemotherapy or Mirvetuximab Soravtansine (MIRV)
Investigator's Choice of Chemotherapy or MIRV given IV.
干预措施: Paclitaxel (Drug)
Part B: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Paclitaxel (Drug)
Part B: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Part A: Chemotherapy or Mirvetuximab Soravtansine (MIRV)
Investigator's Choice of Chemotherapy or MIRV given IV.
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Part C: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Carboplatin (Drug)
Part C: Sofetabart Mipitecan plus Bevacizumab
Administered IV
干预措施: Bevacizumab (Drug)
Part C: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Part B: Sofetabart Mipitecan plus Bevacizumab
Administered IV.
干预措施: Sofetabart Mipitecan (Drug)
Part B: Sofetabart Mipitecan plus Bevacizumab
Administered IV.
干预措施: Bevacizumab (Drug)
Part C: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Paclitaxel (Drug)
Part C: Platinum-based Doublet Chemotherapy plus Bevacizumab
Investigator's choice of platinum doublet chemotherapy IV followed by bevacizumab IV.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator
时间窗: Randomization to radiographic progression or death from any cause (up to 70 months)
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded, Independent, Central Review (BICR)
时间窗: Randomization to radiographic progression or death from any cause (up to 70 months)
Progression-free Survival (PFS)
时间窗: Randomization to radiographic progression or death from any cause (up to 70 months)
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator
次要结局
- Overall Survival (OS)(Randomization to date of death from any cause (up to 70 months))
- PFS(Randomization to radiographic progression or death from any cause (up to 70 months))
- Overall Response Rate (ORR): Proportion of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)(Randomization to disease progression or death (up to 70 months))
- Duration of Response (DOR)(Date of first documented CR or PR to date of radiographic progression or death from any cause (up to 70 months))
- Disease Control Rate (DCR): Proportion of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD)(Randomization to disease progression or death from any cause (up to 70 months))
- PFS2(Randomization to disease progression on next line of treatment or death from any cause (up to 70 months))
- Proportion of Participants with Response of Cancer Antigen-125 (CA-125) per Gynecologic Cancer Intergroup Criteria (GCIG)(Randomization to 30 days post treatment discontinuation)
- Percentage of Assessments with High Side-effect Bother, as measured by Functional Assessment of Cancer Therapy - General Item 5 (FACT GP5)(Randomization to 30 days post treatment discontinuation)
- Change from Baseline in Abdominal/GI Symptoms, as measured by the European Organization for Research and Treatment of Cancer Ovarian Cancer Module (EORTC OV28)(Randomization to 30 days post treatment discontinuation)
- Change from Baseline in Overall Health-related Quality of Life (HRQoL), as measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale(Randomization to 30 days post treatment discontinuation)
- Pharmacokinetics (PK): Minimum Blood Plasma Concentration (Cmin) of LY4170156(Randomization through end of treatment (up to 70 months)])
- Time to Initiation of First Subsequent Systemic Anticancer Therapy or Death (TNTD)(Randomization to initiation of subsequent systemic anticancer or death from any cause (up to 70 months))