Phase 1 Study Evaluating the Safety and PK of ADU-1805 in Advanced Solid Tumors

Официальное название

An Open-Label, Multicenter, Multi-arm Phase 1 Study Evaluating the Safety and Pharmacokinetics of ADU-1805 in Adults With Advanced Solid Tumors

Обзор

This first-in-human, open-label, multicenter, multi-arm dose-escalation study is designed to evaluate the safety, PK, and PD of ADU-1805, an anti- SIRPα monoclonal antibody, as monotherapy and in combination with pembrolizumab (anti-PD-1 antibody).

Подробное описание

This study is designed to evaluate the safety, PK, PD and preliminary clinical activity of ADU-1805, an anti- SIRPα monoclonal antibody, as monotherapy and in combination with pembrolizumab (anti-PD-1 antibody). The study is divided into a dose escalation phase and a dose expansion phase.

The dose expansion phase investigates ADU-1805 plus pembrolizumab at the respective recommended phase 2 dose (RP2D) in four advanced solid tumors: advanced PD-(L)1-naïve MSS colorectal cancer (CRC), PD-1 relapsed/refractory patients with either advanced MSS endometrial cancer (EC), renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC) patients.

Вмешательства

• Препарат ADU-1805
  anti-SIRPα monoclonal antibody
• Препарат Pembrolizumab
  Keytruda

Первичные конечные точки

• Escalation Phase: Incidence and severity of dose limiting toxicity (DLT), treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters [Срок оценки: First 21 days of treatment]
• Expansion Phase: Evaluate the clinical response of ADU-1805 plus pembrolizumab administered as an intravenous (IV) infusion. [Срок оценки: Through study completion, up to 2,5 years]

Вторичные конечные точки (3)

• Escalation and Expansion Phase: Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters [Срок оценки: Through study completion, up to 2,5 years]
• Escalation and Expansion Phase: Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab [Срок оценки: Through study completion, up to 2,5 years]
• Expansion Phase: To confirm safety of ADU-1805 in combination with pembrolizumab as an IV infusion [Срок оценки: Through study completion, up to 2,5 years]

Критерии участия

Критерии включения

• Male or female aged ≥18 years
• Signed and dated informed consent form
• Measurable disease according to RECIST (Safety Expansion only)
• ECOG Performance status of 0 or 1
• Adequate organ and marrow function
• Escalation Phase: Histologically and/or cytologically confirmed diagnosis of metastatic or unresectable solid tumors that are refractory to standard therapy or for which no standard therapy exists
• Expansion Phase: histologically and/or cytologically confirmed diagnosis of advanced PD-(L)1-naïve MSS colorectal cancer (CRC), PD-1 relapsed/refractory patients with either advanced MSS endometrial cancer (EC), renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC) patients, and that have measurable disease according to RECIST

Критерии исключения

• Escalation Phase: Patients that suffer from melanoma, brain tumors, glioblastoma, sarcoma and pancreatic ductal adenocarcinoma (PDAC)
• Expansion Phase:

• > 3 lines of prior systemic treatments
• MSS colorectal cancer (CRC): liver metastasis present
• Pregnancy or breast-feeding
• Prior treatment with or receipt of:

• biological agents, including monoclonal antibodies and immunotherapies, within 28 days prior to the first dose of ADU-1805
• chemotherapy, targeted small molecule therapy, hormonal therapy or radiation therapy within 21 days prior to the first dose of ADU-1805 and within 42 days for nitrosoureas and mitomycin C.
• anti-SIRPα or anti-CD47-directed therapy
• systemic chronic steroid therapy or immunosuppressive therapy within 14 days prior to the first dose of ADU-1805
• other investigational new drug or investigational device within 28 days prior to the first dose of ADU-1805
• vaccine containing live virus within 28 prior to the first dose of ADU-1805
• Active untreated brain metastases
• Active infection requiring systemic therapy
• Impaired cardiac function or clinically significant cardiac disease
• Current Grade >2 toxicity related to prior anti-cancer therapy
• History of drug-induced severe immune-related adverse reaction
• Prior severe hypersensitivity to other monoclonal antibodies or ADU-1805 excipients
• Major surgery within defined period
• Diagnosis or positive test of HIV, hepatitis B, hepatitis C, or active tuberculosis
• Allogenic tissue/solid organ transplant
• Any intercurrent illness that is life-threatening or of such clinical significance that it would interfere with the patient's safety or ability to participate in the study

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 · 4 центра

• Henry Ford Cancer Institute — Detroit
• Washington University Medical Campus — St Louis
• Gabrail Cancer & Research Center — Canton
• Virginia Cancer Specialists — Fairfax

Испания · 2 центра

• Hosp 12 de Octubre — Madrid
• Hospital General Universitario Gergorio Maranon — Madrid

Бельгия · 1 центр

• Grand Hopital de Charleroi (GHdC) - Hopital Notre Dame — Charleroi

Идентификаторы

NCT: NCT05856981 · SRP-22C102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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