Clinical trial NCT06747585: A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Squamous Non-small-cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Cervical Squamous Cell Carcinoma
Esophageal Squamous Cell Carcinoma
Keywords: Claudin-1 Targeted Antibody-Drug Conjugate
Monotherapy
First-in-Human
Recommended Phase 2 dose
Recommended dose for expansion
Lead sponsor: Alentis Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2024-12-24
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.P02 monotherapy in adult patients with selected squamous solid tumors.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Patients with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of Patients with Adverse Events
timeFrame: Screening (day -28 to day -1) up to Safety follow-up (30 ± 5 days post last dose [Up to 3.5 years])
measure: Overall Response Rate (ORR) (Phase I)
timeFrame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
measure: Duration of Response (DoR) (Phase I)
timeFrame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
measure: Overall Response Rate (ORR) (Phase II)
timeFrame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
measure: Duration of Response (DoR) (Phase II)
timeFrame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
Secondary outcomes:
measure: Disease control rate (DCR) (Phase I and II)
timeFrame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
measure: Median Progression-Free Survival (PFS) at 6 and 12 Months (Phase I and II)
timeFrame: At 6 and 12 months after initiation of ALE.P02 treatment
measure: Median Overall Survival (OS) at 6, 12, and 24 Months (Phase I and II)
timeFrame: At 6, 12, and 24 months after initiation of ALE.P02 treatment
measure: Blood Concentration of ALE.P02 Antibody-drug Conjugate (ADC)
timeFrame: Phase I and II: Cycle 1 Day 1 until at end of treatment visit (EoT) (Up to 3.5 years)
measure: Blood Concentration of Total Antibody
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Blood Concentrations of Payload
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Area under the concentration-time curve over the dosing interval (AUCtau)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Maximum Concentration (Cmax)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Minimum concentration (Cmin)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Concentration at the end of a Dosing Interval (Ctrough)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: The terminal elimination rate constant (KeL)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Terminal elimination half-life (t½)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Time of Maximum Concentration (tmax)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Average Concentration (Cavg)
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
measure: Number of Patients with Presence of anti-ALE.P02 Antibodies
timeFrame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia, IRCCS
city: Roma
country: Italy
facility: PU A. Gemelli, Universita Cattolica del Sacro Cuore
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Verona
city: Singapore
country: Singapore
facility: National University Cancer Institue
state: South West
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
state: South West
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: START Hospital HM Nou Delfos
city: Málaga
country: Spain
facility: Hospital Universitario Virgen De La Victoria
city: Taipei
country: Taiwan
facility: Buddihist Tzu Chi Medical Foundation - Taipei Tzu Chi Hospital
Study officials:
References: