A Phase I/IIa open-label, multi-center study to evaluate the safety, tolerability, whole-body distribution, radiation dosimetry and anti-tumor activity of [177Lu]-NeoB administered in patients with advanced solid tumors known to overexpress gastrin-releasing peptide receptor (GRPR).

Advanced Accelerator Applications International S.A., Advanced Accelerator Applications International S.A.4 个研究点分布在 4 个国家目标入组 9 人2024年7月4日

概览

阶段: 1/2 期
干预措施: 未指定
疾病 / 适应症: 未指定
发起方: Advanced Accelerator Applications International S.A., Advanced Accelerator Applications International S.A.
入组人数: 9
试验地点: 4
主要终点: Phase I: Incidence and nature of dose limiting toxicities (DLTs).
状态: 进行中（未招募）
最后更新: 去年

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

Phase I: To identify the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of [177Lu]-NeoB. Phase IIa: Cohorts A, B, C: To assess the anti-tumor activity of [177Lu]-NeoB at the RP2D across different solid tumors; Cohort E: To assess the PK as well as the biodistribution and radiation dosimetry of [177Lu]-NeoB when co-administered with the neprilysin inhibitor (NEPi) LCZ696 in Cycle 1 (only performed in the US and UK).

注册库

euclinicaltrials.eu

开始日期

2024年7月4日

结束日期

待定

最后更新

去年

研究类型

Interventional clinical trial of medicinal product

研究者

发起方

Advanced Accelerator Applications International S.A., Advanced Accelerator Applications International S.A.

入排标准

入选标准

•Signed informed consent must be obtained prior to participation in the study.
•Adult patients (age ≥ 18 years old) with any of the following advanced or metastatic solid tumors: - For Phase I: breast cancer, lung cancer, prostate cancer, GIST, GBM. - For Phase IIa: a. Cohort A: Breast cancer with histology as follows: HR-positive with ER > 10% of nuclei stain, HER-2 negative including HER-2 low as assessed on the primary diagnosis. b. Cohort B: Prostate cancer. c. Cohort C: GIST. d. Cohort D: patients affected by any advanced/metastatic solid tumor type known to overexpress GRPR including recurrent GBM, and with moderate impaired renal function defined as creatinine clearance (calculated using the Cockcroft-Gault formula, or measured) ≥ 30mL/min and < 60mL/min. e. Cohort E: only performed in the US and UK.
•At least one measurable lesion per RECIST 1.1, RANO (applicable for GBM only) criteria detected on the low dose CT or on the MRI (for GBM MRI only) acquired together with the [68Ga]-NeoB PET. The same identified measurable lesion shows [68Ga]-NeoB uptake on PET/CT or PET/MRI. If the only matching lesion is located in the bone, the patient will still be eligible.
•Patients for whom no standard therapy is available, tolerated or appropriate in both Phase I and Phase IIa. Specifically in the Phase IIa breast cancer cohort A, patients need to have completed at least one prior treatment of endocrine therapy (including CDk4/6i) and at least one prior chemotherapy (unless contraindicated) in the metastatic setting. Patients with prior treatment with trastuzumab deruxtecan, alpelisib or elascestrant are also eligible. In case of confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the patient must also have already received a PARP inhibitor based therapy.
•Patient Eastern Cooperative Oncology Group (ECOG performance status: - For phase I: ≤
•For phase IIa: ≤ 1.

排除标准

•Patients who have not had resolution, except where otherwise stated in the inclusion/ exclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for alopecia).
•Patients with history of or ongoing acute or chronic pancreatitis.
•Concurrent bladder outflow obstruction or unmanageable urinary incontinence.
•Administration of a radiopharmaceutical with therapeutic intent within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]-NeoB (IMP2).
•Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow.
•[223Ra]-therapy within the context of diffuse bone or bone-marrow involvement (i.e. "superscan" defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases).
•Patients who have received prior systemic anti-cancer treatment within the following time frames: - Cyclical chemotherapy within a period that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycinC) prior to starting [177Lu]-NeoB treatment. - Biologic therapy (e.g. antibodies), continuous or intermittent small molecule therapeutics, or any other investigational agents within a period which is ≤ 5 T1/2 or ≤ 14 days (whichever is shorter) prior to starting [177Lu]-NeoB treatment.
•History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
•Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to [177Lu]-NeoB treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
•Pregnant or breast-feeding women.

结局指标

主要结局

Phase I: Incidence and nature of dose limiting toxicities (DLTs).

Phase IIa: - Cohorts A, B, C: Individual clinical responses assessed by Response Evaluation Criteria In Solid Tumors (RECIST v1.1). - Cohort E only: only performed in the US and UK.

次要结局

Phase I: • Tissue Activity Curves (ACs) generated from the amount of radioactivity in one given tissue at a given moment over the amount of radioactivity present in the blood at that given moment • Time ACs, describing % of the activity amount injected vs. time will be derived • Absorbed radiation doses of [177Lu]-NeoB in critical organs (e.g. kidneys, bone marrow, pancreas)
Phase I: • Urinary excretion of [177Lu]-NeoB • Half-life of [177Lu]-NeoB in blood • Residence times of [177Lu]-NeoB in organs and tumor lesions • Individual objective response and Duration of Response (DOR)
Phase IIa Cohorts A, B, C: • Absorbed radiation doses of [177Lu]-NeoB in organs and tumor lesions based on TACs • Concentration of [177Lu]-NeoB in blood over time and derived PK parameters • Changes from baseline in EORTC QLQ-C30
Phase IIa Cohort E only: (only performed in the US and UK) • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs • Dose interruptions and modifications
Phase I and IIa: • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs • Dose interruptions and modifications