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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I) [Time frame: Up to 28 days]
• Number of Patients with Adverse Events (Phase I) [Time frame: From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])]
• Overall Response Rate (ORR) (Phase I) [Time frame: 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) [Time frame: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)]
• Overall Response Rate (ORR) (Phase II) [Time frame: 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) [Time frame: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)]

Secondary outcome measures (12)

• Number of Patients with Adverse Events (Phase I RDE and Phase II) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Blood Concentrations of Payload (Phase I and II) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Maximum Concentration (Cmax) (Phase I and II) [Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)]
• Minimum concentration (Cmin) (Phase I and II) [Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 12 centers

• 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
• … and 4 more centers

United States · 9 centers

• 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
• … and 1 more center

Italy · 7 centers

• 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

France · 4 centers

• 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

Netherlands · 3 centers

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

Taiwan · 3 centers

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

Singapore · 2 centers

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

Hong Kong · 1 center

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗