Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer (CRPC)

Официальное название

A Phase 2, Open-label Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer

Обзор

This is a four-part study evaluating the safety and efficacy of a PSMA-directed radioantibody (rosopatamab tetraxetan, conjugated to either In-111 or Ac-225). Part 1 will consist of one administration of In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants then will be enrolled into either Part 2 (Dose Optimization) or Part 3 (Dose Escalation and Expansion) depending on their prior treatment history. Part 4 will be an extended regimen in dose escalation and expansion. Participants qualifying for Part 2 will be randomized to receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle (dose administration on Day 1 and Day 15) at either 45 or 60 kBq/Kg. Participants qualifying for Part 3 must have received prior Lu-177-PSMA-radioligand therapy and will receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at 45, 55, or 60 kBq/Kg. Dose limiting toxicities (DLTs) will be monitored in Part 3 to determine the recommended phase 2 dose (RP2D), and the study may enroll additional participants to be treated with the RP2D dose level. Participants qualifying for Part 4 will initially receive two doses (dose administration on Day 1 and Day 15) at the dose level selected in Part 2, followed by a single third dose of Ac-225 rosopatamab tetraxetan administered approximately 12 weeks after completion of the Part 2 fractionated dosing regimen. The starting dose level for Part 4 will be 22 kBq/kg (or fixed activity equivalent). Dose limiting toxicities (DLTs) will be monitored following administration of the third dose in Part 4 to determine the recommended phase 2 dose (RP2D) of a third dose of Ac-225 rosopatamab tetraxetan. Participants enrolled into any part will attend study visits which will include blood samples, electrocardiogram (ECG), radiographic imaging, and physical examinations along with other assessments.

Вмешательства

• Биопрепарат In-111 rosopatamab tetraxetan
  A single dose of 148 ± 37 MBq In-111 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes.
• Биопрепарат 45 kBq/kg Ac-225 rosopatamab tetraxetan
  45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.
• Биопрепарат 45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.
• Биопрепарат 60 kBq/kg Ac-225 rosopatamab tetraxetan
  60 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.
• Биопрепарат Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  22 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.
• Биопрепарат Single dose 34 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  34 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.
• Биопрепарат Single dose 45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.
• Биопрепарат 55 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  55 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.
• Биопрепарат 60 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan
  60 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Первичные конечные точки

• Part 1: Visual evaluation on whole body planar scans (days 1 and 4) with comparison to reference scans for the presence of radiolabeled rosopatamab textraxetan in organs of interest (e.g., liver, circulation, spleen) to determine biodistribution [Срок оценки: Day 1 and Day 4]
• Part 2: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention [Срок оценки: Screening through Week 12]
• Part 2: Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50) [Срок оценки: Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria]
• Part 3: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention [Срок оценки: Screening through Week 12]
• Part 3: Determine the recommended Phase 2 dose (RP2D) of Ac-225 rosopatamab tetraxetan [Срок оценки: Day 1 through 6 weeks]
• Part 3 (Participants treated at RP2D): Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50) [Срок оценки: Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria]
• Part 4: Incidence of AEs and SAEs overall, by severity, by relationship to study drug, and leading to discontinuation of study intervention [Срок оценки: Screening through Week 12]
• Part 4: Determine the recommended Phase 2 dose (RP2D) of Ac-225 rosopatamab tetraxetan [Срок оценки: Through end of study (approximately 3 years)]

Вторичные конечные точки (9)

• Part 2: Determine the clearance of rosopatamab tetraxetan and Ac-225 rosopatamab tetraxetan via measurement of whole blood and serum levels at specified serial timepoints [Срок оценки: Through Week 8]
• Part 2: Radioactivity levels of Ac-225 rosopatamab tetraxetan [Срок оценки: Through Day 21]
• Part 2: Radiation dosimetry of Ac-225 rosopatamab tetraxetan: Absorbed radiation dose (expressed as Gy/MBq) in normal organs [Срок оценки: Day 1 through Day 15]
• Part 2: Biochemical progression-free survival (bPFS) as assessed by the Prostate Cancer Working Group 3 (PCWG3) [Срок оценки: Through end of study (approximately 3 years) or until disease progression]
• Part 3: Proportion of participants who achieve PSA50 [Срок оценки: Through end of study (approximately 3 years)]
• Part 3: Determine the clearance of rosopatamab tetraxetan and Ac-225 rosopatamab tetraxetan from the circulation via measurement in the serum at specified serial timepoints [Срок оценки: Through Week 8]
• Part 3: Radioactivity levels of Ac-225 rosopatamab tetraxetan [Срок оценки: Through Week 8]
• Part 4: Proportion of participants who achieve PSA50 [Срок оценки: Through end of study (approximately 3 years)]
• Part 4: Biochemical progression-free survival (bPFS) as assessed by the Prostate Cancer Working Group 3 (PCWG3) [Срок оценки: Through end of study (approximately 3 years) or until disease progression]

Критерии участия

Критерии включения

• Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:

• Serum PSA progression as defined by PCWG3 (rising PSA consisting of two consecutive increases measured at least 3 weeks apart, of a rise of >25%, and with an absolute rise of 2.0 ng/mL.
• Soft tissue progression defined as a ≥20% increase in the sum of the diameter (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest sum of the diameter since the previous treatment was started or the appearance of one or more new lesions by CT/magnetic resonance imaging (MRI)
• Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan
• Identification of new soft tissue or bone lesions on PSMA PET imaging
• Metastatic disease defined as either or both of the following:

• Parts 1, 2, 3, and 4: Documented M1 disease on conventional imaging (CT/MRI of the chest/abdomen/pelvis and/or Technetium 99m \[99mTc\] whole-body bone scan)
• Parts 1, 2, and 4 only: Identification of bone lesion(s), extra-pelvic soft tissue lesion(s), or visceral metastases on PSMA PET imaging with an FDA-approved imaging agent
• PSMA PET-positive disease, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions
• Progression following treatment with ADT and at least one ARSI (e.g., enzalutamide, apalutamide, darolutamide, and/or abiraterone acetate)
• The standard of care use (in the setting of metastatic CRPC with significant burden of active bone metastases) of antiresorptive bone-targeted agents (e.g., zoledronic acid, denosumab) is required for all participants without a contraindication, for at least 4 weeks prior to administration of Ac-225 rosopatamab tetraxetan.
• Participants with HIV are eligible if they are well-controlled (i.e, an undetectable HIV viral load (<50 copies/mL) within 6 months of enrollment and a stable ART regimen for at least 6 months prior to enrollment) and at low risk for HIV-related illness

Part 3 Only:

• Prior treatment with Lu-177-PSMA-radioligand therapy
• Prior treatment with up to only one taxane-based chemotherapy regimen is allowed

Критерии исключения

• Superscans by nuclear medicine/99mTc bone scan
• A known malignancy that is progressing or has required active treatment within the past 3 years other than CRPC, which is expected to alter life expectancy or may interfere with CRPC disease assessment
• Prior platinum-based chemotherapy
• Prior PARP inhibitors (e.g., olaparib or rucaparib)
• Prior treatment with Radium-223, Actinium-225, Strontium-89, Samarium-153, Rheunium-186, or Rhenium-188
• Participants receiving anti-coagulants or anti-platelet drugs (e.g., aspirin or nonsteroidal anti-inflammatory drugs \[NSAIDs\]) who cannot discontinue use if platelet count decreases to <50,000

Part 2 and 4 Only:

• Prior chemotherapy for CRPC. Prior taxane chemotherapy for HSPC is allowed if discontinued ≥1 year prior to randomization
• Prior radiopharmaceutical therapy (e.g., Ra-223, Lu-177-PSMA-617, or Lu-177-PSMA-I\&T)
• Prior PSMA-targeted therapy, except for bispecific or CAR-T therapies

Part 3 Only:

• Prior PSMA-targeted therapy (e.g., antibody-drug conjugates or CAR-T therapy), except for Lu-177-PSMA-radioligand therapy and bispecific or CAR-T therapies

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• University of California San Diego — San Diego
• Dana-Farber Cancer Institute — Boston
• Washington University in St. Louis — St Louis
• X Cancer Omaha / Urology Cancer Center — Omaha
• Laura & Isaac Perlmutter Cancer Center — New York
• Memorial Sloan Kettering Cancer Center — New York
• New York Presbyterian/Weill Cornell Medical Center — New York
• Duke University Medical Center — Durham
• … и ещё 1 центр

Идентификаторы

NCT: NCT06549465 · CONVERGE-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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