A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

Официальное название

GUARDIAN-101: A Phase 1 Dose Escalation and Expansion Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

Обзор

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A\*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.

Подробное описание

This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CLSP-1025 when administered to HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation. The study will be conducted in 2 parts: Part A Monotherapy Dose Escalation to determine the recommended dose(s) for expansion (RDE\[s\]) and Part B Monotherapy Expansion to explore the preliminary antitumor activity as well as further characterize the safety, tolerability, PK, and PD of CLSP-1025 at the RDE(s).

Вмешательства

• Препарат CLSP-1025
  CLSP-1025 will be administered by IV infusion

Первичные конечные точки

• Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s]) [Срок оценки: 28 days after infusion]
• Part B: Evaluate the Objective response rate (ORR) of CLSP-1025 as a monotherapy in HLA-selected patients with advanced solid tumors that express the p53 R175H mutation [Срок оценки: Up to 24 months after infusion]

Вторичные конечные точки (12)

• Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0 [Срок оценки: Up to 24 months after infusion]
• Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0 [Срок оценки: Up to 24 months after infusion]
• Number of patients with clinically significant changes in QTcF Interval [Срок оценки: Up to 24 months after infusion]
• Maximum plasma concentration (Cmax) of CLSP-1025 [Срок оценки: Pre-dose and up to 168 hours post-dose]
• Minimum plasma concentration (Cmin) of CLSP-1025 [Срок оценки: Pre-dose and up to 168 hours post-dose]
• Area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025 [Срок оценки: Pre-dose and up to 168 hours post-dose]
• Half-life (t1/2) of CLSP-1025 [Срок оценки: Pre-dose and up to 168 hours post-dose]
• Assess the immunogenicity of CLSP-1025 [Срок оценки: Up to 24 months after infusion]
• Part A: Objective Response Rate (ORR) [Срок оценки: Up to 24 months after infusion]
• Duration of response (DOR) [Срок оценки: Up to 24 months after infusion]
• Time to Response [Срок оценки: Up to 24 months after infusion]
• Disease Control Rate [Срок оценки: Up to 24 months after infusion]

Критерии участия

Критерии включения

• Patients must be at least 18 years of age at the time of signing the informed consent.
• Patients must be willing and able to provide written informed consent
• Patients must have locally advanced or metastatic solid tumors that have progressed after standard of care therapy or for which no standard therapy exists
• Tumors must harbor a TP53 R175H variant mutation confirmed by an accredited laboratory-based test
• Patients must be HLA-A\*02:01 positive by central assay
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
• Adequate hematological, renal and hepatic function
• Per Investigator judgement, patient is willing and able to complete study visits and/or procedures per the protocol and comply with study requirements for study participation

Критерии исключения

• Patients with Li-Fraumeni syndrome or other known germline p53 R175H mutation
• Patients who have received other p53 R175H-directed therapies
• Patients who have not fully recovered from adverse events due to previous anticancer therapies
• Patients with active infection requiring systemic antimicrobial therapy
• Any other primary malignancy within the 2 years prior to enrollment (except for non- melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or prostate cancer in remission.
• Known active central nervous system metastases and/or carcinomatous meningitis

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 · 21 центр

• HonorHealth Research Institute — Scottsdale
• The University of Arizona Cancer Center — Tucson
• USC - Norris Comprehensive Cancer Center — Los Angeles
• University of California Davis Comprehensive Cancer Center — Sacramento
• University of California San Francisco — San Francisco
• University of Miami - Sylvester Comprehensive Cancer Center — Miami
• The University of Chicago Comprehensive Cancer Center — Chicago
• University of Kentucky Markey Cancer Center — Lexington
• … и ещё 13 центров

Идентификаторы

NCT: NCT06778863 · CLSP-1025-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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