Clinical trial NCT06054477: Study of ALE.C04 in Patients With Head and Neck Cancer
Official title: A Phase I/II, Open-Label, Multi-Center Study of ALE.C04 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Keywords: Immunotherapy
Anti-Claudin1
ALE.C04
Phase I/II
Lead sponsor: Alentis Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2023-09-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1 will consist of i) a dose escalation of ALE.C04 monotherapy evaluating approximately 3 dose levels of ALE.C04, ii) a dose escalation of ALE.C04 and pembrolizumab combination evaluating approximately 2 dose levels of ALE.C04 and iii) a randomized two RDEs evaluating two dose level of ALE.C04 combined with pembrolizumab to establish Recommended Phase 2 Dose (RP2D).

Phase 2 will consist of a 1:1 randomized 2 arms comparing ALE.C04 (at the RP2D dose determined in the phase 1) combined to pembrolizumab with pembrolizumab alone.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety profile of ALE.C04 monotherapy and in combination with pembrolizumab, to characterize pharmacokinetics profile of ALE.C04, recommended Phase II dose (RP2D) for ALE.C04 in combination with pembrolizumab and to assess anti-tumor activity of ALE.C04 in combination with pembrolizumab in patients with Head and Neck Cancer.

Detailed description: The study comprises a phase I and a phase II. The phase I dose escalation part for both ALE.C04 monotherapy and in combination with pembrolizumab and a recommended dose for expansion (RDE) part for ALE.C04 in combination with pembrolizumab. The phase II comprises a 1:1 randomized 2 arms assessing ALE.C04 and pembrolizumab given in combination versus pembrolizumab monotherapy

Eligibility criteria: Inclusion Criteria:

1. Be willing and able to provide written informed consents
2. Be 18 years of age on day of signing informed consent.
3. Have histologically or cytologically confirmed Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) that is considered incurable by local therapies.
4. Have provided tissue for claudin-1 (CLDN1), programmed death ligand-1 (PD-L1) and biomarker analysis in a central Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
5. Have measurable disease based on RECIST 1.1 as determined by the site.
6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
7. Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer

Exclusion Criteria:

1. Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC (Phase II randomized combination part only).
2. Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or patient has not fully recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered treatment. Palliative radiotherapy to a limited field is allowed.
3. Severe immune-related adverse events leading to discontinuation of prior immune-oncology agent only for Phase I dose escalation monotherapy and combination and Phase II monotherapy.
4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
5. Dermatological conditions requiring active pharmacological treatment including psoriasis, atopic dermatitis, excessively dry skin or recurrent conjunctivitis, scleroderma, vitiligo, or any other active autoimmune dermatological disorder.
6. 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, in the opinion of the treating investigator.
7. Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1 or anti-PD-L2 (Phase II randomized combination part only).

Primary outcomes:
measure: Incidence of Dose Limiting Toxicity (DLT)
timeFrame: 21 days
measure: Incidence and severity of adverse events (AEs), serious adverse events (SAEs)
timeFrame: Up to 30 days after last dose - Approximately 4.5 years
measure: Confirmed Objective Response Rate (ORR) by investigators assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Up to 4.5 year
measure: Confirmed Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment according to RECIST1.1
timeFrame: Up to 4.5 year
Secondary outcomes:
measure: Confirmed ORR by investigators assessment according to RECIST1.1
timeFrame: up to 4.5 year
measure: Confirmed immune Objective Response Rate (iORR) by investigators assessment according to immune RECIST
timeFrame: up to 4.5 year
measure: Disease Control Rate (DCR) as per investigator assessment according to RECIST1.1
timeFrame: up to 4.5 years
measure: Immune Disease Control Rate (iDCR) as per investigator assessment according to immune RECIST
timeFrame: up to 4.5 years
measure: Duration Of Response (DOR)
timeFrame: up to 4.5 years
measure: Immune Duration Of Response (iDOR)
timeFrame: up to 4.5 years
measure: Progression Free Survival (PFS) evaluated by investigators
timeFrame: up to 4.5 years
measure: Immune Progression Free Survival (iPFS) evaluated by investigators
timeFrame: up to 4.5 years
measure: Overall Survival (OS)
timeFrame: up to 4.5 years
measure: Maximum serum concentration (Cmax) pharmacokinetics (PK) of ALE.C04
timeFrame: up to 4.5 years
measure: Minimum serum concentration (Cmin) pharmacokinetics (PK) of ALE.C04
timeFrame: up to 4.5 years
measure: Area under the concentration-time curve (AUC) pharmacokinetics (PK) of ALE.C04
timeFrame: up to 4.5 years
measure: Maximum serum concentration (Cmax) Pharmacokinetics (PK) of pembrolizumab
timeFrame: up to 4.5 years
measure: Minimum serum concentration (Cmin) Pharmacokinetics (PK) of pembrolizumab
timeFrame: up to 4.5 years
measure: Area under the concentration-time curve (AUC) Pharmacokinetics (PK) of pembrolizumab
timeFrame: up to 4.5 years
measure: Immunogenicity of ALE.C04
timeFrame: up to 4.5 years
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30
timeFrame: Phase II combination part only - Up to 4.5 year
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Question Head and Neck module 43 (HN43)
timeFrame: Phase II combination part only - Up to 4.5 year
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California USC Norris Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University Yale Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Lake Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
state: Ontario
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre
city: Toulouse
country: France
facility: Oncopole Claudius Regaud, Iuct-Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hong Kong
country: Hong Kong
facility: Prince Of Wales Hospital
city: Candiolo
country: Italy
facility: Candiolo cancer Center,FPO IRCCS
state: Piedmont
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia S.R.L.
city: Milan
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori Di Milano
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Barcelona
country: Spain
facility: Vall d&#39;Hebron Institute of Oncology
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Valencia
country: Spain
facility: Incliva Biomedical Research Institute - Hospital Clinico Universitario Valencia
city: Bern
country: Switzerland
facility: Inselspital, University Hospital Bern
Study officials:
References: