A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid Tumors

Официальное название

A Phase I/II, Open-Label, Multicenter Study of ALE.P02 (Claudin-1 Targeted Antibody-Drug Conjugate) as a Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+Squamous Solid Tumors

Обзор

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P02 monotherapy in adult patients with selected squamous solid tumors.

Подробное описание

This Study has a Phase I ALE.P02 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P02 as monotherapy at RP2D in adult patients with selected advanced or metastatic Claudin-1 positive (CLDN1+) cancers.

Вмешательства

• Препарат ALE.P02
  ALE.P02, will be administered by IV infusion according to the assigned arms.

Первичные конечные точки

• Number of Patients with Dose Limiting Toxicities (DLTs) [Срок оценки: Up to 28 days]
• Number of Patients with Adverse Events [Срок оценки: Screening (day -28 to day -1) up to Safety follow-up (30 ± 5 days post last dose [Up to 3.5 years])]
• Overall Response Rate (ORR) (Phase I) [Срок оценки: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)]
• Duration of Response (DoR) (Phase I) [Срок оценки: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)]
• Overall Response Rate (ORR) (Phase II) [Срок оценки: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)]
• Duration of Response (DoR) (Phase II) [Срок оценки: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)]

Вторичные конечные точки (12)

• Disease control rate (DCR) (Phase I and II) [Срок оценки: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)]
• Median Progression-Free Survival (PFS) at 6 and 12 Months (Phase I and II) [Срок оценки: At 6 and 12 months after initiation of ALE.P02 treatment]
• Median Overall Survival (OS) at 6, 12, and 24 Months (Phase I and II) [Срок оценки: At 6, 12, and 24 months after initiation of ALE.P02 treatment]
• Blood Concentration of ALE.P02 Antibody-drug Conjugate (ADC) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at end of treatment visit (EoT) (Up to 3.5 years)]
• Blood Concentration of Total Antibody [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Blood Concentrations of Payload [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Area under the concentration-time curve over the dosing interval (AUCtau) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Maximum Concentration (Cmax) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Minimum concentration (Cmin) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]
• Concentration at the end of a Dosing Interval (Ctrough) [Срок оценки: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)]

Критерии участия

Критерии включения

• Have disease and treatment history as: Have histologically or cytologically confirmed advanced locally recurrent and inoperable or metastatic SqNSCLC, HNSCC (nasopharyngeal cancer included), ESCC or CSCC.
• Phase I Dose Escalation: Have received at least one systemic standard of care regimen and being refractory or intolerant to the treatment.
• Phase I RDE and Phase II: Have received no more than 2 lines of systemic standard of care regimen and being refractory or intolerant to the treatment.
• Have provided tissue for CLDN1 analysis in a central laboratory.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
• Demonstrate adequate bone marrow and organ function.
• Patients must have recovered from all toxicities led by prior treatment.
• Have measurable disease based on RECIST 1.1 as determined by the site.

Критерии исключения

• Diagnosed with cancers of predominantly non-squamous histology (eg, adenosquamous carcinoma) or adenocarcinoma.
• Has received antineoplastic therapies prior to study intervention within specified time frame.
• Has rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain).
• Patients with uncontrolled diabetes.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has clinically significant gastrointestinal bleeding and has an active infection requiring systemic treatment and has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study, interfere with the patient's participation for the full duration of the clinical study, or is not in the best interest of the patient to participate.
• Concomitant use of drugs that are known to prolong or shorten QT and/or have known risk of Torsades de Pointes.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 9 центров

• START Madrid- Centro Integral Oncologico Clara Campal — PAU de Sanchinarro
• Hospital Universitario Quironsalud Madrid — Pozuelo de Alarcón
• NEXT Oncology Barcelona — Barcelona
• Hospital Universitari Vall D Hebron — Barcelona
• START Hospital HM Nou Delfos — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario Virgen De La Victoria — Málaga
• Hospital Universitario Virgen De La Macarena — Seville
• … и ещё 1 центр

США · 8 центров

• Mayo Foundation for Medical Education and Research - Mayo Cl — Scottsdale
• Providence Medical Foundation — Fullerton
• USC Norris Comprehensive Cancer Center — Los Angeles
• Yale Comprehensive Cancer Center — New Haven
• The University of Chicago Medical Center - Oncology — Chicago
• Norton Cancer Institue Downtown — Louisville
• Hackensack University Medical Center — Hackensack
• NEXT Oncology Virginia — Fairfax

Италия · 7 центров

• Istituto Clinico Humanitas — Milan
• Ospedale San Raffaele, IRCCS — Milan
• Istituto Nazionale del Tumori, Fondazione IRCCS — Milan
• IEO - Istituto Europeo di Oncologia, IRCCS — Milan
• Ospedale Santa Maria delle Croci di Ravenna Oncologia — Ravenna
• PU A. Gemelli, Universita Cattolica del Sacro Cuore — Roma
• Centro Ricerche Cliniche Verona — Verona

Франция · 6 центров

• Institut Bergonie — Bordeaux
• Centre Georges Francois Leclerc - Oncologie Medicale — Dijon
• CHRU De Lille- Hôpital Claude Huriez - Medical Oncology — Lille
• AP-HM Hôpital de La Timone CEPCM — Marseille
• Centre Hospitalier Universitaire (CHU) de Toulouse - IUCT Oncopole — Toulouse
• Institut Gustave Roussy — Villejuif

South Korea · 4 центра

• National Cancer Center — Goyang-si
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center - Oncology — Seoul

Тайвань · 4 центра

• Changhua Christian Medical Foundation Changhua Christian Hospital — Changhua
• Changhua Christian Medical Foundation Changhua Christian Hospital — Changhua
• National Taiwan University Hospital — Taipei
• Buddihist Tzu Chi Medical Foundation - Taipei Tzu Chi Hospital — Taipei

Сингапур · 2 центра

• National University Cancer Institue — Singapore
• National Cancer Centre Singapore — Singapore

Гонконг · 1 центр

• Chinese University of Hong Kong - Prince of Wales Hospital — Shatin

Идентификаторы

NCT: NCT06747585 · ALE.P02.01 · 2024-515459-39-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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