A Study of [177Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642 With [68Ga]Ga-A9-6217 or [177Lu]Lu-A9-0631 Imaging in GRPR+ Solid Tumors

Официальное название

A Phase 1-1b Study to Evaluate the Safety, Efficacy, and Dosimetry of [177Lu]Lu-A9-0631, [225Ac]Ac-A9-0642, and [68Ga]Ga-A9-6217 in Participants With GRPR+ Tumors

Обзор

This is a Phase 1-1b multicenter clinical study to evaluate the safety, efficacy, and dosimetry of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-0642 in participants with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors.

Подробное описание

This is a multicenter, open-label Phase 1-1b study of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642 in subjects with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors.

The study consists of two parts (Phase 1 and 1b).

Phase 1 is the dose escalation portion of the study. The aim of the Phase 1 is to evaluate the safety and tolerability as well as the normal organ and tumor dosimetry of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642, and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).

Phase 1b will be the dose expansion portion of the study. The aim of the Phase 1b will be to further evaluate the safety, efficacy, and normal organ and tumor dosimetry of \[177 Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642 administered at the RP2D in subjects with (1) Locally advanced, unresectable, or metastatic HR+/HER2- breast cancer; (2) Locally advanced, unresectable, or metastatic prostate cancer; (3) Locally advanced, unresectable, or metastatic CRC; and (4) Other locally advanced, unresectable, or metastatic GRPR-positive solid tumors.

Вмешательства

• Диагностический тест [68Ga]Ga-A9-6217
  Administered IV
• Диагностический тест Low dose [177Lu]Lu-A9-0631
  Administered IV
• Препарат [177Lu]Lu-A9-0631
  Administered IV
• Препарат [225Ac]Ac-A9-0642
  Administered IV

Первичные конечные точки

• Phase 1-1b: Incidence of Adverse Events by Frequency, Duration, and Severity [Срок оценки: From the first dose of study drug up to the End of Treatment (30 days after the last dose)]
• Phase 1: Number of Patients with Dose-Limiting Toxicities (DLTs). [Срок оценки: Up to 28 days following first study treatment]
• Phase 1: Maximum tolerated dose (MTD) [Срок оценки: Up to 28 days following first study treatment]

Вторичные конечные точки (2)

• Phase 1-1b: Absorbed dose estimates (Gy) in normal organs for [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642 [Срок оценки: Up to 7 days after each injection for up to 6 cycles (each cycle is 28 days)]
• Phase 1-1b: Objective Response Rate (ORR) [Срок оценки: Every 8 ± 1 weeks until radiographic disease progression or up to 12 months after the last dose of [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642]

Критерии участия

Критерии включения

• Participant has provided written informed consent prior to any study-specific procedure.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have measurable target lesion per RECIST v1.1.
• Progression from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care therapies and have one of the following locally advanced or metastatic tumor types: prostate cancer; HR+/HER2- breast cancer; colorectal cancer; and GRPR-positive solid tumors.
• Have GRPR-expressing disease as confirmed by PET / CT or SPECT imaging.
• Adequate organ function within 14 days of first administration of investigational therapeutic product.
• At least 4 weeks from prior major surgery.

Критерии исключения

• Received anticancer treatment including but not limited to chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) or 5 half-lives, (t1/2) whichever is shorter, to the administration of therapeutic investigational product.
• History of uncontrolled allergic reactions and/or known or expected hypersensitivity to a peptide-based imaging or therapeutic agent or any excipient present in either of the therapeutic investigational products.
• Major surgery within 4 weeks of planned first dose of the therapeutic investigational product.
• Prior external beam radiation therapy to more than 25% of the bone marrow.
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• Any active infection.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 2 центра

• Melbourne Theranostic Innovation Center — Melbourne N.
• GenesisCare Murdoch — Murdoch

Идентификаторы

NCT: NCT07661641 · A9-0600-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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