Phase 0/1 Study of the Safety and Tolerability of 177Lu-RAD204, a Lutetium-177 Radiolabelled Single Domain Antibody Against Programmed Cell Death-Ligand 1 in Patients With Metastatic Solid Tumours
概览
- 阶段
- 早期 1 期
- 干预措施
- 177Lu-RAD204
- 疾病 / 适应症
- 未指定
- 发起方
- Radiopharm Theranostics, Ltd
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Time Activity Curves (TACs)
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability, biodistribution, radiation dosimetry and preliminary anti-tumour activities of 177Lu-RAD204 in participants with selected solid tumours, to identify the MTDs/ recommended doses of 177Lu-RAD204 for future exploration.
The study will consist of a Pre-screening Period (if applicable for PD-L1 testing), a Screening Period of up to 4 weeks, followed by a Phase 0 (Imaging) Period for imaging and dosimetry to 177Lu-RAD204im and a Phase I (Treatment) Period for 177Lu-RAD204tr dose escalation.
详细描述
This is a first in human, Phase 0/1, open-label study of 177Lu-RAD204 consisting of an Imaging Period with 177Lu-RAD204im (imaging dose) and a Treatment Period with 177Lu-RAD204tr (treatment dose) to determine the recommended dose(s) for future exploration of 177Lu-RAD204 in participants with PDL1+ advanced solid tumors. Screening Period: Screening Period of up to 4 weeks. Phase 0 (Imaging Period): Low dose (10mCi) of 177Lu-RAD204 administered on Imaging Day 1 with a follow-up period of up to 2 weeks to assess imaging, safety and dosimetry. The dose may be increased, if needed, to improve image quality. Phase 1 (treatment Period): 177Lu-RAD204tr dose escalation * Treatment Period with each cycle lasting 6 weeks. Extension of the planned dose intervals are possible following discussion and agreement between the Sponsor and Investigator. * Participants may be treated with multiple cycles, as long as they appear to derive clinical benefit as determined by the Investigator and provided there is adequate clinical safety and organ dosimetry data. * Dose Limiting Toxicity (DLT) observation period for 177Lu-RAD204tr is 6 weeks following the first injection of 177Lu-RAD204tr. * Should an alternative treatment schedule be explored, the DLT observation period for 177Lu-RAD204tr at that dose level will be the proposed cycle duration.
研究者
入排标准
入选标准
- •Willing and able to provide informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
- •Adult participants ≥ 18 years of age.
- •Participants with a documented history of histopathologically confirmed relapsed/refractory locally advanced, inoperable or metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high with documented disease progression during or after their most recent line of anticancer therapy. Participants must be refractory to or have refused standard of care therapy (including PD-1/PD-L1 inhibitors) or have refused or have no standard of care therapy available that is likely to provide clinical benefit.
- •Participants with PD-L1 positive NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high:
- •If the participant tumour's PD-L1 expression status is unknown, PD-L1 positivity may be determined in a pre-screening step whereby the participant may be approached to provide written informed consent to have their tumour tissue undergo IHC testing as determined by a validated test (tumour tissue may be obtained from archived samples or from a freshly obtained biopsy).
- •Any number of prior treatment lines are allowed.
- •Must have at least 1 measurable target lesion according to RECIST version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Participants must have a life expectancy of ≥ 4 months in the opinion of the Investigator.
- •Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants \< 50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with luteinising hormone (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status.
排除标准
- •History of prior organ transplant.
- •Any other known, active malignancy, except for treated cervical intraepithelial neoplasia or non-melanoma skin cancer. Patients with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with study Sponsor, if it is determined not to put the patient at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
- •Have any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures such as participants with severe claustrophobia who are unresponsive to oral anxiolytics, participants with low back pain who cannot lie comfortably on an imaging table, participants who are hyperactive or hyperkinetic such that they cannot tolerate lying still for multiple time point imaging procedures, etc.
- •Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia).
- •History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics, 177Lu-RAD204 or any of its excipients.
- •Inadequate organ functions as reflected in laboratory parameters:
- •Creatinine clearance or body surface area (BSA) adjusted estimated glomerular filtration rate (eGFR) (calculated using any clinically validated formula, preferably Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or measured) \< 60 mL/min
- •Platelet count of \< 80 × 109/L
- •Absolute neutrophil count (ANC) \< 1.5 × 109/L
- •Haemoglobin \< 9 g/dL
研究组 & 干预措施
177Lu-RAD204
Single-arm, open-label study of 177Lu-RAD204 consisting of a Phase 0 Imaging Period (Im) and a Phase 1 Treatment Period (Tr).
干预措施: 177Lu-RAD204
结局指标
主要结局
Time Activity Curves (TACs)
时间窗: 72 hours
Percent of the injected activity vs time for selected organs and tumors
Biokinetics of 177Lu-RAD204im
时间窗: 72 hours
Time-integrated activity coefficients of 177Lu-RAD204im in organs and tumor lesions
Pharmacokinetics of 177Lu-RAD204im
时间窗: 72 hours
Half-life of 177Lu-RAD204im in blood
Radiation dosimetry of Lu177-RAD204im
时间窗: 72 hours
Absorbed radiation doses of 177Lu-RAD204im in critical organs (e.g., kidneys, bone marrow)
Recommended dose(s) of 177Lu-RAD204tr for future exploration
时间窗: 6 weeks
Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD204tr injection cycle of treatment
Safety and tolerability of 177Lu-RAD204tr
时间窗: 6 weeks
The properties, incidence, nature and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
次要结局
- Recommended dose(s) of 177Lu-RAD204im for future exploration(2 weeks)
- Preliminary antitumor activity of 177Lu-RAD204tr(Up to 30 weeks)
- Safety and tolerability of a single dose of 177Lu-RAD204im(6 weeks)
- Radiation dosimetry of 177Lu-RAD204tr(72 hours)