A Study to Investigate ALE.P03 as Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+ Solid Tumors

Официальное название

A Phase I/II, Open-label, Multicenter Study of ALE.P03 (Claudin-1 Targeted Antibody-drug Conjugate) as a Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+ 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.P03 monotherapy in adult patients with selected squamous solid tumors.

Подробное описание

This Study has a Phase I ALE.P03 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P03 as monotherapy at RP2D in adult patients with selected advanced or metastatic Claudin-1 positive (CLDN1+) cancers.

Вмешательства

• Препарат ALE.P03
  ALE.P03, will be administered by IV infusion according to the assigned arms.
• Препарат ALE.P03
  ALE.P03, will be administered by IV infusion according to the assigned arms.
• Препарат ALE.P03
  ALE.P03, will be administered by IV infusion according to the assigned arms.

Первичные конечные точки

• Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I) [Срок оценки: Up to 28 days]
• Number of Patients with Adverse Events (Phase I) [Срок оценки: From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])]
• Overall Response Rate (ORR) (Phase I) [Срок оценки: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years)]
• Duration of Response (DoR) (Phase I) [Срок оценки: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)]
• Overall Response Rate (ORR) (Phase II) [Срок оценки: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years)]
• Duration of Response (DoR) (Phase II) [Срок оценки: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)]

Вторичные конечные точки (12)

• Number of Patients with Adverse Events (Phase I RDE and Phase II) [Срок оценки: From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years]]
• Disease control rate (DCR) (Phase I and II) [Срок оценки: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years)]
• Median Progression-Free Survival (PFS) rate at 6 and 12 Months (Phase I and II) [Срок оценки: At 6 and 12 months after initiation of ALE.P03 treatment]
• Median Overall Survival (OS) rate at 6, 12, and 24 Months (Phase I and II) [Срок оценки: At 6, 12, and 24 months after initiation of ALE.P03 treatment]
• Blood Concentration of ALE.P03 Antibody-drug Conjugate (ADC) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at end of treatment visit (EoT) (Up to 4 years)]
• Blood Concentrations of Total Antibody (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Blood Concentrations of Payload (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Area under the concentration-time curve over the dosing interval (AUCtau) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Maximum Concentration (Cmax) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Minimum concentration (Cmin) (Phase I and II) [Срок оценки: Phase I and II: From Day 1 until at EoT (Up to 4 years)]

Критерии участия

Критерии включения

• Have histologically and cytologically metastatic confirmed advanced or metastatic colorectal cancer, intrahepatic cholangiocarcinoma, squamous non-small cell lung cancer, urothelial carcinoma, and cervical squamous cell carcinoma.
• Have documented radiological disease progression at study entry.
• Have provided tissue for CLDN1 (Claudin-1) analysis in a central laboratory.

Phase I Dose Escalation:

\- Received and being refractory/intolerant to available systemic standard of care (SOC) regimens (based on local institutional guidelines) for advanced disease.

Phase I RDE and Phase II:

• Received 1-2 available systemic SOC regimens (based on local institutional guidelines) for advanced disease and being refractory or intolerant to treatment.
• Patients with actionable oncogenic drivers: received feasible targeted therapy.

Applicable for Phase I Dose Escalation, Phase I RDE and Phase II:

• Measurable disease per RECIST 1.1, as determined by the site.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Groups Performance Status.
• Demonstrate adequate bone marrow and organ function as per the protocol.

Критерии исключения

• SqNSCLC and CSCC: diagnosed with a tumor of predominantly non-squamous histology result or adenocarcinoma.
• Has received antineoplastic therapies prior to study intervention within specified time frame.
• Has rapidly progressing disease.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has a history of (non-infectious) interstitial lung disease/pneumonitis that required steroids or current symptomatic or clinically significant pneumonitis requiring steroids and/or immunosuppressive therapies.
• Has clinically significant gastrointestinal bleeding.
• Has an active infection requiring systemic treatment.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical 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

Испания · 12 центров

• Hospital HM Nou Delfos — Barcelona
• Vall d'Hebron University Hospital — Barcelona
• See outside Hospital Universitario Reina Sofia — Córdoba
• Virgen of Arrixaca University Clinical Hospital — El Palmar
• Ramón y Cajal Hospital — Madrid
• Hospital Universitario Fundación Jiménez Díaz — Madrid
• HM Sanchinarro University Hospital — Madrid
• University Hospital Quironsalud Madrid — Madrid
• … и ещё 4 центра

США · 9 центров

• Mayo Clinic Comprehensive Cancer Center — Phoenix
• USC Norris Comprehensive Cancer Center — Los Angeles
• Yale Comprehensive Cancer Center — New Haven
• The University of Chicago Medical Center - Oncology — Chicago
• Norton Cancer Institute - Norton Healthcare Pavilion — Louisville
• John Theurer Cancer Center — Hackensack
• MD Anderson Cancer Center — Houston
• Next Oncology-Oncology — San Antonio
• … и ещё 1 центр

Италия · 7 центров

• Oncologo presso Ospedale ASST Grande Ospedale Metropolitano Niguarda — Milan
• Ospedale San Raffaele, IRCCS - Oncologia Medica — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• IEO - Istituto Europeo di Oncologia, IRCCS — Milan
• Ravenna - Ospedale S. Maria delle Croci — Ravenna
• IRCCS Istituto Clinico Humanitas di Rozzano — Rossano
• Policlinico Santa Maria alle Scotte, Azienda Ospedaliero Universitaria Senese - Immunotera — Siena

Франция · 4 центра

• Centre Georges Francois Leclerc - Oncologie Medicale — Dijon
• CHU La Timone — Marseille
• Centre Hospitalier Universitaire (CHU) de Toulouse - Institut Universitaire du Cancer de T — Toulouse
• Institut Gustave Roussy (IGR) — Villejuif

Нидерланды · 3 центра

• The Netherlands Cancer Institute (NKI) — Amsterdam
• Radboudumc - Centrum voor Oncologie — Nijmegen
• Erasmus University Medical Center — Rotterdam

Тайвань · 3 центра

• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei
• Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Oncology — Taoyuan

Сингапур · 2 центра

• National University Hospital (NUH) - Medical Oncology — Singapore
• National Cancer Centre Singapore (NCCS) — Singapore

Гонконг · 1 центр

• Prince of Wales Hospital (PWH) - The Chinese University of Hong Kong (CUHK) — Гонконг

Идентификаторы

NCT: NCT07169734 · ALE.P03.01 · 2025-521441-24-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗