RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07169734Sponsor: Alentis Therapeutics AGLast updated: 2026-03-19

Summary

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.

Arms & interventions

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

Outcome measures

Primary

Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I)
DLTs as defined in the protocol will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
Time frame: Up to 28 days
Number of Patients with Adverse Events (Phase I)
Adverse events will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
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)
The ORR is the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) This is assessed to establish RP2D for ALE.P03 (Phase I RDE)
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)
The DoR is defined for patients achieving a CR or PR as per Investigator review according to RECIST 1.1 to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P03 (Phase I RDE).
Time frame: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)
Overall Response Rate (ORR) (Phase II)
The ORR is assessed to assess anti-tumor activity of ALE.P03 (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)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to assess anti-tumor activity of ALE.P03 (Phase II).
Time frame: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)

Secondary

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)
Concentration at the end of a dosing interval (Ctrough) (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
The terminal elimination rate constant (KeL) (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
Terminal elimination half-life (t½) (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
Time of Maximum Concentration (tmax) (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
Average Concentration (Cavg) (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
Number of Patients with Presence of anti-ALE.P03 Antibodies (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)
Number of Patients with Positive anti-ALE.P03 Antibodies (Phase I and II)
Time frame: Phase I and II: From Day 1 until at EoT (Up to 4 years)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.