LuX: A Feasibility Study of Xaluritamig in Participants With Metastatic Castrate Resistant Prostate Cancer and Suboptimal Response to Lutetium 177 Vipivotide Tetraxetan
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- Proportion of Participants who achieve Partial or Complete Response or PSA90
研究概览
简要总结
This is a phase 2a, open label, single arm, multi-site study of xaluritamig in mCRPC patients following treatment with ≥1 ARPI, taxane chemotherapy (if eligible) and stable or partial PSA response following 2 cycles of lutetium 177 vipivotide tetraxetan.
Participants will continue treatment until clinical or radiographic progression of disease, withdrawal, or toxicity requiring discontinuation of therapy. All participants will be evaluated for overall response per RECIST v1.1,8 radiographic progression free survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) criteria, and PSA response. Approximately 30 participants will be enrolled. There is no data on response with alternative treatments following lutetium 177 vipivotide tetraxetan against which to benchmark the response rate. This phase 2a study will serve as an exploratory pilot to determine if a larger phase 2b study is warranted in this setting.
详细描述
Primary Objective and Endpoints
To evaluate the efficacy of xaluritamig following lutetium 177 vipivotide tetraxetan in patients with mCRPC, using a composite endpoint defined as the proportion of participants who achieve either of the following:
- Partial or complete response up to 24 weeks by local investigator's assessment per RECIST v1.1 in participants with baseline measurable disease, with confirmation at least 4 weeks after the initial observation; OR
- PSA90, defined as a decline of ≥ 90% from baseline PSA (for participants with a baseline PSA ≥ 2.0 ng/mL) up to 24 weeks, confirmed by a subsequent PSA value obtained ≥3 weeks later.
Secondary Objectives and Endpoints
To evaluate the safety and efficacy of xaluritamig following lutetium 177 vipivotide tetraxetan in patients with mCRPC as measured by:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be included in this study, participants should complete all screening procedures and meet all of the following criteria (i.e., evaluations performed as part of routine care prior to informed consent can be used for screening and eligibility confirmation):
- •Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
- •NOTE: Privacy authorization may be either included in the informed consent or obtained separately.
- •18 years of age and above
- •Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- •Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
- •Received ≥1 novel ARPI (e.g., enzalutamide, darolutamide, apalutamide and/or abiraterone).
- •Eastern Cooperative Oncology Group (ECOG) status of 0-2 (Appendix A).
- •Life expectancy of >6 months.
- •Previously treated with, declined treatment with, or are considered unsuitable/unwilling for taxane regimen per investigator discretion.
- •Prior completion of 2 cycles of lutetium 177 vipivotide tetraxetan between 16 and 6 weeks prior to initiation of study treatment, with evidence of PSA response between 0-90% decrease from the pre- lutetium 177 vipivotide tetraxetan baseline, documented by a PSA measurement obtained within 4 weeks of second dose of lutetium 177 vipivotide tetraxetan.
- •Participants must have either:
- •baseline measurable disease per RECIST v1.1 at time of screening or
- •baseline PSA ≥ 2 ng/mL at time of screening.
- •Patients must have adequate organ function:
- •a. Bone marrow reserve: i. White blood cell (WBC) count ≥2.5 x 10⁹ /L OR absolute neutrophil count (ANC) ≥1.5 x 10⁹/L ii. Platelets ≥75 x 10⁹ /L iii. Hemoglobin ≥9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L) b. Hepatic: iv. AST and ALT ≤ 3 X upper limit of normal (ULN) (or ≤ 5 X ULN for participants with liver involvement) v. total bilirubin (TBL) ≤ 1.5 X ULN (or ≤ 2 X ULN for participants with liver involvement). For patients with known Gilbert's Syndrome, < 3 X ULN is permitted.
- •c. Renal: estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation ≥ 30 ml/min/1.73 m
- •d. Pulmonary Function: Baseline oxygen saturation > 92% on room air at rest and no oxygen supplementation.
- •e. Cardiac function: Left ventricular ejection fraction > 50% (screening echocardiography only required in subjects with known history of cardiac disease, prior MI, angina pectoris, coronary artery bypass graft (CABG), angioplasty, stent placement).
- •Participants with partners of childbearing potential must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study including 6 months after the last dose of study drug. Sperm donation is prohibited during the study and for 6 months after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
排除标准
- •Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments in the judgment of the site Principal Investigator (PI). Participants with prior history of malignancy that have been adequately treated and who have been disease-free for > 3 years are eligible, as are subjects with adequately treated non-melanoma skin cancer or superficial bladder cancer.
- •Requirement for chronic systemic corticosteroid therapy (prednisone dose >10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing. Corticosteroid treatment for adverse event management as described in Section 6.1.10 is allowed.
- •Previous PSMA-targeted radioligand therapy, aside from treatment with 2 cycles of lutetium 177 vipivotide tetraxetan, is not allowed.
- •Prior PSMA radioligand therapy within 6 weeks of first dose of study treatment.
- •Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.
- •Untreated central nervous system metastases or leptomeningeal disease, symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- •Active systemic infection treated with IV antibiotics within 7 days prior to the first dose of study drugs.
- •Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are permitted.
- •History or evidence of inflammatory bowel disease (ulcerative colitis or Chron disease) or any other gastrointestinal disorder causing chronic nausea, vomiting or diarrhea (CTCAE ≥ grade 2).
- •Evidence of interstitial lung disease or active, non-infectious pneumonitis, or uncontrolled asthma.
- •Recent history of arterial (e.g. stroke or transient ischemic attack) or venous (e.g., pulmonary embolism or deep vein thrombosis) thrombosis; within 12 and 6 months prior to first dose of study treatment, respectively.
- •Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as determined by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia prolongation > 480 ms, electrolyte disturbances, etc), or patients with congenital long QT syndrome.
- •Recent history of myocardial infarction and/or symptomatic congestive hear failure (New York Heart Association ≥ class II) within 12 months of first dose of study treatment, with the exception of ischemia or non ST segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of study treatment.
- •Unresolved toxicities from prior anti-tumor therapy not having resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or less, with the exception of alopecia, neuropathy, endocrinopathy, xerostomia, or toxicities that are stable and well-controlled.
- •Known allergy to any of the compounds under investigation.
- •Any other condition which, in the opinion of the investigator, would preclude participation in this trial.
研究组 & 干预措施
Arm 1: Xaluritamig
Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.
干预措施: Xaluritamig (Drug)
结局指标
主要结局
Proportion of Participants who achieve Partial or Complete Response or PSA90
时间窗: Baseline to 24 weeks
Proportion of participants with mCRPC treated with xaluritamig after lutetium-177 vipivotide tetraxetan who achieve either: (1) a confirmed Complete Response (CR) or Partial Response (PR) within 24 weeks by local investigator assessment per RECIST v1.1 in participants with baseline measurable disease, with confirmation ≥4 weeks after initial response; or (2) a confirmed PSA90 response, defined as a ≥90% decline from baseline PSA in participants with baseline PSA ≥2.0 ng/mL within 24 weeks, confirmed by a subsequent PSA assessment obtained ≥2 weeks later. RECIST v1.1 classifies tumor response as CR (disappearance of all target lesions), PR (≥30% decrease in tumor size), Stable Disease (SD), or Progressive Disease (PD; ≥20% increase in tumor size or new lesions). Higher response rates indicate greater treatment efficacy.
次要结局
- Radiographic Progression-Free Survival (rPFS)(Up to 2 years post-treatment)
- Duration of response (DOR)(From Baseline measurable disease until the first date that progressive disease is objectively documented, assesed up to 58 months.)
- Time to Prostate-Specific Antigen (PSA) response (30%, 50%, 70%, and 90%)(assessed up to 58 months)
- Time to Prostate-Specific Antigen (PSA) Progression(From start of study treatment until documented PSA progression, assessed up to 58 months)
- Duration of PSA 50/90 response(assessed up to 58 months)
- Number of Treatment-Emergent Adverse Events (TEAE) following treatment initiation(Up to 3 years)