NCT05670106已完成2 期
A Prospective, Open-label, Multi-center, Single-arm, Phase II Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 18
- 主要终点
- Main part: Confirmed Overall Response Rate (ORR) per Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study was to assess the efficacy, safety, tolerability, Pharmacokinetic(s) (PK) and dosimetry of [177Lu]Lu-PSMA-617 when administered in addition to Best Supportive/Best Standard of Care (BSC/BSoC) in Chinese participants with progressive PSMA-positive mCRPC who received at least 1 novel androgen receptor pathway inhibitor (ARPI) and were previously treated with 1 to 2 taxane regimens. Furthermore, the safety, PK, and dosimetry of [68Ga]Ga-PSMA-11 were assessed.
Data from this study will be used to bridge global pivotal phase III study (VISION, AAA617A12301) and to support China registration of [177Lu]Lu-PSMA-617 as a novel anticancer modality, namely radioligand therapy, in mCRPC.
详细描述
This was a 2-part study:
- Main part: Thirty participants with at least 1 measurable lesion by PCWG3-modified RECIST v1.1 criteria were enrolled in the main part. The primary endpoint of confirmed overall response rate (ORR) was analyzed with participants in this part and was assessed via independent centralized review of radiographic images provided by the Investigator and as outlined in PCWG3-modified RECIST v1.1 criteria.
- Extension part: The extension part enrolled additional 30 participants with or without measurable lesions following the main part. The secondary endpoints were analyzed with all participants in both main part and extension part.
Screening and enrollment period:
Written informed consent form (ICF) was obtained prior to any screening procedures. All screening procedures described in the Assessment Schedule were completed within 28 days prior to enrollment, except for radiographic imaging assessment, which was done within 21 days prior to enrollment.
The participants were assessed for eligibility and underwent a mandatory [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan to evaluate Prostate-specific Membrane Antigen (PSMA) positivity for eligibility as assessed by central readers. Only participants with PSMA positive cancer and confirmed eligibility criteria were enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •Participants must be Chinese male adults >= 18 years of age.
- •Participants must have histological, pathological, and/or cytological confirmation of prostate cancer.
- •Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader according to the VISION read rules.
- •Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dl, or < 1.7 nmol/L).
- •Participants must have received at least one ARPI (such as enzalutamide and/orabiraterone).
- •Participants must have been previously treated with at least 1, but no more than 2 previous taxane regimens.
- •A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a participant has received only 1 taxane regimen, the participant is eligible if: the participants' physician deems him unsuitable to receive a second taxane regimen (e.g., frailty assessed by geriatric or health status evaluation or intolerance, etc.)
- •Documented progressive mCRPC, based on at least 1 of the following criteria:
- •Serum/plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week apart, the minimal start value is 2.0 ng/ml
- •Soft-tissue progression defined based on PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)
- •Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)
- •Participants must have >= 1 metastatic lesion that is present on baseline CT, MRI or bone scan imaging obtained =< 21 days prior to enrollment via central reading.
- •In main part: participant must have at least one measurable lesion by PCWG3-modified RECIST v1.1 via central reading
- •Participants must have adequate organ function:
- •Bone marrow reserve:
- •White blood cell (WBC) count >= 2.5 × 109/L OR absolute neutrophil count (ANC) >= 1.5 × 109/L
- •Platelets >=100 × 109/L
- •Hemoglobin >= 9 g/dL
- •Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome =< 3 × ULN is permitted
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3.0 × ULN OR =< 5.0 × ULN for participants with liver metastases
- •eGFR >= 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
- •Albumin >3.0 g/dL.
排除标准
- •Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
- •Previous PSMA-targeted radioligand therapy.
- •Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies], APRI is not included) within 28 days prior to day of enrollment.
- •Any investigational agents (e.g. poly adenosine diphosphate-ribosyl polymerase inhibitors [PARPi]) within 28 days prior to day of enrollment.
- •History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
- •Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
- •Transfusion for the sole purpose of making a subject eligible for study inclusion.
- •Participants with a history of central nervous system (CNS) metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
- •Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids.
- •Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
- •Symptomatic spinal cord compression, or clinical or radiologic findings indicative of impending cord compression.
研究组 & 干预措施
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Experimental
Patients received the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) could be used.
干预措施: Best supportive/best standard of care (BS/BSOC) (Other)
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Experimental
Patients received the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) could be used.
干预措施: 68Ga-PSMA-11 (Drug)
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Experimental
Patients received the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) could be used.
干预措施: [177Lu]Lu-PSMA-617 (Drug)
结局指标
主要结局
Main part: Confirmed Overall Response Rate (ORR) per Blinded Independent Central Review (BICR)
时间窗: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, approx. 1 year
Confirmed Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR is based on PCWG3-modified RECIST v1.1 response for patients with measurable disease at baseline.
次要结局
- Main & extension parts: Overall response rate (ORR)(From date of randomization till radiographic progression or date of death from any cause.)
- Main & extension parts: Radiographic progression free survival (rPFS)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first.)
- Main & extension parts: Overall survival (OS)(From date of randomization until date of death from any cause.)
- Main & extension parts: Disease control rate (DCR)(From date of randomization till radiographic progression or date of death from any cause.)
- Main & extension parts: Duration of response (DOR)(From date of randomization until date of progression or date of death from any cause.)
- Main & extension parts: Time to a first symptomatic skeletal event (TTSSE)(From date of randomization till date of a first SSE or date of death from any cause.)
- Main & extension parts: PSA50 response rate(From date of randomization till end of long-term FU.)
- Main & extension parts: Progression Free Survival (PFS)(From date of randomization until date of progression or date of death from any cause, whichever come first.)
- Main & extension parts: European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L)(From date of randomization till the end of long term FU)
- Main & extension parts: Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire(From date of randomization till 30 day safety follow-up or at the end of long term FU for patients prematurely discontinued, assessed up to 57 months (estimated final OS analysis))
- Main & extension parts: Brief Pain Inventory - Short Form (BPI-SF) Questionnaire(From date of randomization till the end of long term FU)
- Main & extension parts: Number of Participants with Treatment Emergent Adverse Events(From day of the first administration of study treatment to 30 days after EOT or to the last [177Lu]Lu-PSMA-617 dose date + 41 days, whichever is later.)
- Main & extension parts: Area under the blood concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-PSMA-617(Cycle 1 Week 1(Day 1) and Cycle 1 Week 2(Day 8): Pre dose, 0(End of infusion), 20 & 60 mins(+/- 5 mins), 2 & 4 hours(+/-30 mins), 24 hours(+/- 2 hr), 48 hours(+/- 4 hr), 72 hours(+/- 6 hr), 168 hours(+/- 12 hr) from the end of infusion (1 cycle=42 days))
- Main & extension parts: Observed maximum blood concentration (Cmax) of [177Lu]Lu-PSMA-617(Cycle 1 Week 1(Day 1) and Cycle 1 Week 2(Day 8): Pre dose, 0(End of infusion), 20 & 60 mins(+/- 5 mins), 2 & 4 hours(+/-30 mins), 24 hours(+/- 2 hr), 48 hours(+/- 4 hr), 72 hours(+/- 6 hr), 168 hours(+/- 12 hr) from the end of infusion (1 cycle=42 days))
- Main & extension parts: Blood concentration of [177Lu]Lu-PSMA-617(Cycle 1 Week 1(Day 1) and Cycle 1 Week 2(Day 8): Pre dose, 0(End of infusion), 20 & 60 mins(+/- 5 mins), 2 & 4 hours(+/-30 mins), 24 hours(+/- 2 hr), 48 hours(+/- 4 hr), 72 hours(+/- 6 hr), 168 hours(+/- 12 hr) from the end of infusion (1 cycle=42 days))
- Main & extension parts: Organ absorbed dose of [177Lu]Lu-PSMA-617(Cycle 1 Week 1(Day 1) and Cycle 1 Week 2(Day 8): 1~2 & 4 hours, 18~26 hours, 48 hours(+/- 12 hr), 168 hours(+/- 12 hr) from the end of infusion (1 cycle=42 days))
- Main & extension parts: Area under the blood concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [68Ga]Ga-PSMA-11(Screening (Day -42 to Day -14) : 5 mins (+/- 3 mins), 15 & 30 & 45 mins (+/- 5 mins), 85 mins (+/- 10 mins), 175 & 245 mins (+/- 30 mins) from the end of infusion)
- Main & extension parts: Observed maximum blood concentration (Cmax) of [68Ga]Ga-PSMA-11(Screening (Day -42 to Day -14) : 5 mins (+/- 3 mins), 15 & 30 & 45 mins (+/- 5 mins), 85 mins (+/- 10 mins), 175 & 245 mins (+/- 30 mins) from the end of infusion)
- Main & extension parts: Blood concentration of [68Ga]Ga-PSMA-11(Screening (Day -42 to Day -14) : 5 mins (+/- 3 mins), 15 & 30 & 45 mins (+/- 5 mins), 85 mins (+/- 10 mins), 175 & 245 mins (+/- 30 mins) from the end of infusion)
- Main & extension parts: Organ absorbed dose of [68Ga]Ga-PSMA-11(Screening (Day -42 to Day -14): 30 mins (+/- 5 mins), 60 mins (+/- 10 mins), 120 mins (+/- 20 mins) and 255 mins (+/- 30 mins) from the end of infusion)
研究者
研究点 (18)
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