A Phase 1-1b Study to Evaluate the Safety, Efficacy, and Dosimetry of [177Lu]Lu-A9-0631, [225Ac]Ac-A9-0642, and [68Ga]Ga-A9-6217 in Participants With GRPR+ Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 115
- 试验地点
- 2
- 主要终点
- Phase 1-1b: Incidence of Adverse Events by Frequency, Duration, and Severity
研究概览
简要总结
This is a Phase 1-1b multicenter clinical study to evaluate the safety, efficacy, and dosimetry of [177Lu]Lu-A9-0631 and [225Ac]Ac-0642 in participants with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors.
详细描述
This is a multicenter, open-label Phase 1-1b study of [177Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642 in subjects with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors.
The study consists of two parts (Phase 1 and 1b).
Phase 1 is the dose escalation portion of the study. The aim of the Phase 1 is to evaluate the safety and tolerability as well as the normal organ and tumor dosimetry of [177Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642, and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).
Phase 1b will be the dose expansion portion of the study. The aim of the Phase 1b will be to further evaluate the safety, efficacy, and normal organ and tumor dosimetry of [177 Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642 administered at the RP2D in subjects with (1) Locally advanced, unresectable, or metastatic HR+/HER2- breast cancer; (2) Locally advanced, unresectable, or metastatic prostate cancer; (3) Locally advanced, unresectable, or metastatic CRC; and (4) Other locally advanced, unresectable, or metastatic GRPR-positive solid tumors.
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
- •Participant has provided written informed consent prior to any study-specific procedure.
- •Age ≥ 18 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Have measurable target lesion per RECIST v1.
- •Progression from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care therapies and have one of the following locally advanced or metastatic tumor types: prostate cancer; HR+/HER2- breast cancer; colorectal cancer; and GRPR-positive solid tumors.
- •Have GRPR-expressing disease as confirmed by PET / CT or SPECT imaging.
- •Adequate organ function within 14 days of first administration of investigational therapeutic product.
- •At least 4 weeks from prior major surgery.
排除标准
- •Received anticancer treatment including but not limited to chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) or 5 half-lives, (t1/2) whichever is shorter, to the administration of therapeutic investigational product.
- •History of uncontrolled allergic reactions and/or known or expected hypersensitivity to a peptide-based imaging or therapeutic agent or any excipient present in either of the therapeutic investigational products.
- •Major surgery within 4 weeks of planned first dose of the therapeutic investigational product.
- •Prior external beam radiation therapy to more than 25% of the bone marrow.
- •Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- •Any active infection.
研究组 & 干预措施
Phase 1B Dose Expansion
干预措施: [225Ac]Ac-A9-0642 (Drug)
Phase 1 Dose Escalation
干预措施: [68Ga]Ga-A9-6217 (Diagnostic Test)
Phase 1 Dose Escalation
干预措施: [225Ac]Ac-A9-0642 (Drug)
Phase 1B Dose Expansion
干预措施: [68Ga]Ga-A9-6217 (Diagnostic Test)
Phase 1B Dose Expansion
干预措施: Low dose [177Lu]Lu-A9-0631 (Diagnostic Test)
Phase 1B Dose Expansion
干预措施: [177Lu]Lu-A9-0631 (Drug)
Phase 1 Dose Escalation
干预措施: Low dose [177Lu]Lu-A9-0631 (Diagnostic Test)
Phase 1 Dose Escalation
干预措施: [177Lu]Lu-A9-0631 (Drug)
结局指标
主要结局
Phase 1-1b: Incidence of Adverse Events by Frequency, Duration, and Severity
时间窗: From the first dose of study drug up to the End of Treatment (30 days after the last dose)
An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of patients experiencing an AE in Part 1 will be reported.
Phase 1: Number of Patients with Dose-Limiting Toxicities (DLTs).
时间窗: Up to 28 days following first study treatment
DLTs is defined as any predefined AE occurring during the DLT observation period.
Phase 1: Maximum tolerated dose (MTD)
时间窗: Up to 28 days following first study treatment
Incidence of dose-limiting toxicity (DLT) per dose level of \[177Lu\]Lu-A9-0631 and/or \[225Ac\]Ac-A9-0642.
次要结局
- Phase 1-1b: Absorbed dose estimates (Gy) in normal organs for [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642(Up to 7 days after each injection for up to 6 cycles (each cycle is 28 days))
- Phase 1-1b: Objective Response Rate (ORR)(Every 8 ± 1 weeks until radiographic disease progression or up to 12 months after the last dose of [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642)