A Dose Escalation and Dose Optimization Phase 1a/1b Study to Evaluate Safety, Tolerability and Dosimetry of Radioligand Therapy With LY4337713 in Adults With FAP-Positive Solid Tumors (FiREBOLT)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 241
- 试验地点
- 49
- 主要终点
- Phase 1a: Percentage of Participants with Dose Limited Toxicity (DLT) Toxicities
研究概览
简要总结
This is a study of LY4337713 in participants with certain types of cancer that is advanced or has spread. Participants must have cancer with high levels of a protein called fibroblast activation protein (FAP). The purpose of this study is to evaluate safety, side effects, and efficacy of LY4337713. In addition, this study will evaluate how much LY4337713 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. For each participant, the study will last about 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Must have clinical or imaging evidence of fibroblast activation protein (FAP) expression per local assessment
- •Must have histologically or cytologically confirmed diagnosis of one of the following:
- •Adenocarcinoma of the pancreas
- •Hormone receptor (HR)-positive human epidermal growth factor 2 (HER2)-negative breast cancer
- •HER2-positive breast cancer
- •Triple negative breast cancer (TNBC)
- •Platinum-resistant or refractory ovarian cancer (including ovarian carcinosarcoma)
- •Other solid tumors
- •Gastric cancer (adenocarcinoma)
- •Colorectal cancer (CRC)
- •Esophageal cancer (squamous cell carcinoma or adenocarcinoma)
- •Cholangiocarcinoma
- •Must have received prior treatments as indicated below:
- •Adenocarcinoma of the pancreas: Participants must have received at least 1, but no more than 2 prior regimens for locally advanced unresectable or metastatic disease.
- •HR-positive HER2-negative breast cancer: Participants must have received less than or equal to (≤)5 prior lines of treatment for advanced or metastatic disease, which must include a cyclin-dependent kinase 4/6 inhibitor.
- •HER2-positive breast cancer: Participants must have received at least 2 lines of HER2-targeted therapy, which should include at least 1 antibody-drug conjugate (ADC) for metastatic disease (if locally available).
- •TNBC: Participants must have received at least 2 lines of therapy for metastatic disease.
- •Platinum-resistant or refractory ovarian cancer: Participants must have received or after at least 1 platinum-based therapy.
- •Other solid tumors (gastric cancer, CRC, esophageal and cholangiocarcinoma): Participants must have received greater than or equal to (≥)1 prior line of systemic therapy for advanced or metastatic disease; including prior line(s) in combination with immunotherapy or vascular endothelial growth factor inhibitor.
- •Phase 1b:
- •Participants must have advanced or metastatic solid tumors and have received ≥1 prior line of therapy.
- •Must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to
- •Measured creatinine clearance ≥60 milliliters per minute (mL/min)
排除标准
- •Have known active central nervous system (CNS) metastases or carcinomatous meningitis.
- •Have significant cardiovascular disease
- •Have prolongation of the corrected QTcF >470 milliseconds (msec) during screening. QTcF is calculated using Fridericia's Formula: QTcF = QT/(RR0.33)
- •Have evidence of ongoing and untreated urinary tract obstruction
- •Had previous hemi- or total-body radiation.
- •Had previous adoptive T-cell therapy (e.g., chimeric antigen receptor T-cell [CAR-T therapy, T-cell receptor [TCR] therapy, etc.)
- •Unable to lie flat during, or otherwise tolerate, single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT) or magnetic resonance imaging (MRI).
研究组 & 干预措施
Experimental LY4337713 (Cohort C)
Tumor specific cohort will receive LY4337713 administered IV.
干预措施: LY4337713 (Drug)
Experimental: LY4337713 (Cohort D)
Tumor specific cohort will receive LY4337713 administered IV.
干预措施: LY4337713 (Drug)
LY4337713 (Cohort A1)
Escalating doses of LY4337713 administered intravenously (IV).
干预措施: LY4337713 (Drug)
LY4337713 (Cohort E)
Tumor specific cohort will receive LY4337713 administered IV.
干预措施: LY4337713 (Drug)
LY4337713 (Cohort A2)
Two or more dose regimens of LY4337713 (evaluated during dose escalation) administered IV.
干预措施: LY4337713 (Drug)
Experimental: LY4337713 (Cohort B)
Tumor specific cohort will receive LY4337713 administered IV.
干预措施: LY4337713 (Drug)
结局指标
主要结局
Phase 1a: Percentage of Participants with Dose Limited Toxicity (DLT) Toxicities
时间窗: Cycle 1 (28 days)
Phase 1b: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
时间窗: Baseline through imaging follow-up, up to 5 years
Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
次要结局
- Phase 1a: Absorbed Dose Estimates (Gy) in Normal Organs(Baseline through Cycle 4 Day 4 (Cycle = 4 or 6 weeks))
- Phase 1a: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4337713(Cycle 1 Day 1 up to Cycle 2 Day 4 post dose (Cycle = 4 or 6 weeks))
- Phase 1a: PK: Area Under the Concentration Time Curve (AUC) of LY4337713(Cycle 1 Day 1 up to Cycle 2 Day 4 post dose (Cycle = 4 or 6 weeks))
- Phase 1a: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)(Baseline through imaging follow-up, up to 1 year)
- Phase 1a: Number of Participants with Best Overall Response (BOR)(Baseline through imaging follow-up, up to 1 year)
- Phase 1a and 1b: Duration of Response (DOR)(Baseline through imaging follow-up, up to 5 years)
- Phase 1a and 1b: Time to Response (TTR)(Baseline through imaging follow-up, up to 1 year)
- Phase 1a and 1b: Percentage of Participants with Disease Control Rate (DCR)(Baseline through imaging follow-up, up to 1 year)