68Ga-PSMA-0057 and 177Lu-PSMA-0057 in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer

Официальное название

A Phase I/II, Single-Arm, Open-Label, Dose-Escalation and Expansion Study of 68Ga-PSMA-0057 and 177Lu-PSMA-0057 in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer

Обзор

This is a single-arm, open-label, Phase I/II clinical study designed to evaluate the safety, tolerability, pharmacokinetics, dosimetry, pharmacodynamics, and preliminary efficacy of Gallium \[68Ga\] PSMA-0057 Injection and Lutetium \[177Lu\] PSMA-0057 Injection as an integrated theranostic regimen in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The study consists of a Phase I dose-escalation phase to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of 177Lu-PSMA-0057, followed by a Phase II dose-expansion phase to further evaluate preliminary antitumor efficacy and confirm safety and pharmacologic profiles. Eligible participants will receive 68Ga-PSMA-0057 for PET imaging and 177Lu-PSMA-0057 for radioligand therapy. Key objectives include characterization of safety, tolerability, pharmacokinetics, dosimetry, pharmacodynamics, and preliminary therapeutic activity.

Вмешательства

• Препарат 68Ga-PSMA-0057
  68Ga-PSMA-0057 IV administered as imaging agent for PET/CT.
• Препарат 177Lu-PSMA-0057
  177Lu-PSMA-0057 radiopharmaceutical solution for injection.

Первичные конечные точки

• Incidence of adverse events [68Ga-PSMA-0057] [Срок оценки: 3 days]
• Incidence of adverse events [177Lu-PSMA-0057] [Срок оценки: up to 2 years]
• Incidence of dose limiting toxicities [177Lu-PSMA-0057] [Срок оценки: 6 weeks]
• Preliminary efficacy: PSA50 response rate (Phase II) [Срок оценки: up to 2 years]

Критерии участия

Критерии включения

• Able to communicate well with investigators, understand the study purpose and requirements, voluntarily participate, and sign written informed consent.
• Male, ≥18 years at screening.
• Histologically or cytologically confirmed prostate cancer (excluding neuroendocrine prostate cancer and small cell prostate cancer), previously treated with at least one novel hormonal agent and 1-2 taxane-based regimens, or deemed intolerant to taxanes.
• Serum/plasma testosterone at castrate level (<50 ng/dL or <1.7 nmol/L).
• Documented progressive mCRPC based on ≥1 of the following: PSA progression (two consecutive PSA rises ≥1 week apart from a minimum value of 2.0 ng/mL); soft tissue progression per PCWG3 and RECIST v1.1; or bone progression with ≥2 new lesions.
• PSMA-positive on imaging with 68Ga-PSMA-0057 (within 3 days before treatment start) or other investigator-accepted PSMA tracers (within 6 months before treatment start), using criteria in Section 4.8.5.
• At least one measurable lesion per RECIST v1.1 and/or at least one bone metastasis per PCWG3.
• Estimated life expectancy ≥12 weeks.
• ECOG performance status 0-1 at baseline.
• Adequate organ and bone marrow function, meeting the following lab criteria:

1)Bone Marrow: Absolute Neutrophil Count (ANC) ≥1.5×109/L, Platelets (PLT) ≥100×109/L, White Blood Cell (WBC) count ≥2.5×109/L, Hemoglobin (HGB) ≥9.0 g/dL (no transfusions/growth factors within 14 days prior to screening).

2)Liver Function: Serum Total Bilirubin (T-Bil) ≤1.5 ULN (unless Gilbert's syndrome); Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≤3 ULN for non-liver metastasis, or ≤5 ULN for liver metastasis.

3)Renal Function: Serum creatinine ≤1.5 ULN, or estimated Glomerular Filtration Rate (eGFR) ≥50 mL/min/1.73m2 (calculated using the MDRD formula).

11.Serum albumin concentration ≥30 g/L 12.Toxicities from prior therapies recovered to CTCAE v5.0 Grade 0-1 (alopecia excepted).

13.Men with reproductive potential agree to use highly effective contraception from informed consent through 6 months after last study dose and have no plans to donate sperm.

Критерии исключения

• History of hypersensitivity to any study drug component or excipients, or history of specific allergic disease requiring systemic therapy, or other serious allergic reactions.
• Prior PSMA-targeted radioligand therapy, or treatment with radionuclides such as Sr-89, Sm-153, Re-186, Re-188, Ra-223, or hemibody radiation within 6 months prior to consent.
• Use of any investigational drug or device within 30 days before consent.
• Systemic anticancer therapy within 28 days or 5 half-lives prior to consent (whichever is longer), including chemotherapy, radiotherapy, immunotherapy, targeted therapy, systemic immunomodulatory drugs, or antitumor traditional Chinese medicines/formulations within 2 weeks before first dose.
• Another malignancy within the past 5 years, except for curatively treated cervical carcinoma in situ, non-melanoma skin cancers, etc.
• Major surgery or significant traumatic injury within 4 weeks before consent.
• Active brain metastases or CNS involvement, including untreated symptomatic lesions or those requiring radiation, surgery, or steroids within 1 month prior to screening.
• Symptomatic spinal cord compression or clinical/imaging findings suggestive of impending cord compression.
• Severe arterial/venous thromboembolic events within 6 months prior to screening; history of stroke; uncontrolled hypertension; decompensated heart failure (NYHA III-IV); LVEF <50%; unstable angina; clinically significant arrhythmias requiring intervention.
• Significant acute or chronic infections, including active TB, systemic bacterial or fungal infections requiring systemic therapy.
• Clinically significant COPD or moderate-severe chronic respiratory disease requiring systemic therapy within 6 months before first dose.
• Uncontrolled bladder outlet obstruction or incontinence (patients managed effectively with standard measures are allowed).
• Active autoimmune disease requiring systemic treatment within the past 2 years or likely to recur, or active peptic ulcer disease or bleeding disorders.
• History of solid organ transplantation or allogeneic hematopoietic stem cell transplantation (corneal transplant recipients not requiring immunosuppressants may be included).
• Syphilis, HIV infection, HCV (HCV antibody positive with detectable HCV RNA), or active HBV infection (HBsAg positive with HBV DNA ≥ULN).
• Contraindications to PET-CT or SPECT-CT imaging, or factors deemed by the investigator to preclude adequate imaging acquisition and interpretation.
• Any condition judged by the investigator likely to interfere with compliance or study participation, or impair the ability to give informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07310355 · SRT007-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗