An Open-label, Multicentre, Integrated Phase 1 & 2 Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Anti-tumour Activity of Lutetium (177Lu) rhPSMA-10.1 Injection in Men With Metastatic Castrate-resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 82
- 试验地点
- 24
- 主要终点
- Phase 1 Incidence of DLTs
研究概览
简要总结
To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
详细描述
This is an interventional, open-label, integrated Phase 1 & 2 study to assess the safety, tolerability, radiation dosing regimen and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 (IMP) in men with metastatic castrate-resistant prostate cancer (mCRPC). The study will consist of 2 parts: a non-randomised Phase 1 part, with safety, dose-finding, and dosimetry components, and a randomised Phase 2 part, with efficacy and safety assessments, and testing dosing regimens selected following analysis of the safety and dosimetry data in Phase 1. Both phases will include subjects with prostate-specific membrane antigen (PSMA)-positive mCRPC, which has progressed following prior therapy. Phase 1 will include a post-chemotherapy mCRPC cohort of subjects who have experienced disease progression on or after at least 1 novel androgen axis drug (NAAD) (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. Phase 2 will include subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide) but have not received previous taxane-based chemotherapy for the treatment of mCRPC.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
- •Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
- •Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and/or presence of disease on full body 99mTc bone scan performed within 28 days of screening.
- •Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
- •At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
- •Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
- •Prior major surgery must be at least 12 weeks prior to study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
- •Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
- •Adequate contraception for patients and their partners.
- •For Phase 1 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. For Phase 2 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide), but have not received previous taxane-based chemotherapy for the treatment of mCRPC.
排除标准
- •Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
- •Presence of significant PSMA-negative disease on ceCT/MRI scan
- •Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
- •Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
- •Known history of haematological malignancy.
- •Known history of central nervous system (CNS) metastases.
- •Histological findings consistent with neuroendocrine phenotype of prostate cancer.
- •Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
- •Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
- •Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
- •Ongoing treatment with bisphosphonates for bone-targeted therapy.
- •Severe urinary incontinence that would preclude safe disposal of radioactive urine.
- •Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator.
- •Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
- •Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
- •Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
- •Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.
- •Transfusion of blood products for the sole purpose of meeting the eligibility criteria for this clinical study.
- •Participation in other studies involving IMP(s) within 28 days or 5 half-lives (whichever is longer) prior to study entry and/or during study participation.
研究组 & 干预措施
Phase 1, Cohort A
Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).
干预措施: Lutetium (177Lu) rhPSMA-10.1 Injection (Drug)
Phase 1, Cohort A
Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).
干预措施: 18F-rhPSMA-7.3 injection (in phase 1 only) (Diagnostic Test)
Phase 1, Cohort B
Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).
干预措施: Lutetium (177Lu) rhPSMA-10.1 Injection (Drug)
Phase 1, Cohort B
Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).
干预措施: 18F-rhPSMA-7.3 injection (in phase 1 only) (Diagnostic Test)
Phase 2, Cohort 2A
Subjects with PSMA positive disease will receive 2 doses at 10.00 GBq (270 mCi) followed by up to 5 additional doses at 7.40 GBq (200 mCi), all doses administered at 6-weekly intervals.
干预措施: Lutetium (177Lu) rhPSMA-10.1 Injection (Drug)
Phase 2, Cohort 2B
Subjects with PSMA positive disease will receive up to 8 doses at 7.40 GBq (200 mCi). The first 3 doses will be administered at 3-weekly intervals, with the remaining doses being administered at 6-weekly intervals.
干预措施: Lutetium (177Lu) rhPSMA-10.1 Injection (Drug)
Phase 2, Cohort 2C (optional)
If opened, subjects with PSMA positive disease will receive 2 doses at 14.80 GBq (400 mCi) followed by up to 4 additional doses at 7.40 GBq (200 mCi), all doses administered at 6-weekly intervals.
干预措施: Lutetium (177Lu) rhPSMA-10.1 Injection (Drug)
结局指标
主要结局
Phase 1 Incidence of DLTs
时间窗: 6 weeks post final IMP
Incidence of DLTs during the DLT observation period.
Phase 1 Frequency and nature of TEAEs
时间窗: End of study
Frequency and nature of treatment-emergent adverse events (TEAEs).
Phase 2 Evaluate the efficacy of Lutetium (177Lu) rhPSMA-10.1 Injection
时间窗: 6 weekly intervals
The number of subjects with an anti-tumour response defined as ≥50% reduction in PSA level from baseline to the end of treatment.
次要结局
未报告次要终点