Study of ALE.C04 in Patients With Head and Neck Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: ALE.C04; Drug: Pembrolizumab

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • University Health Network, Princess Margaret Cancer Centre
• France
  • Bordeaux, France, 33075
    • Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre
  • Toulouse, France, 31059
    • Oncopole Claudius Regaud, IUCT-Oncopole
  • Villejuif, France
    • Institut Gustave Roussy
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei tumori di Milano
  • Milano, Italy, 20141
    • Istituto Europeo Di Oncologia S.r.l.
  • Piedmont
    • Candiolo, Piedmont, Italy, 10060
      • Candiolo cancer Center,FPO IRCCS
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 168583
    • National Cancer Centre Singapore
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Madrid, Spain
    • MD Anderson Cancer Center
  • Santiago De Compostela, Spain
    • Hospital Clínico Universitario de Santiago de Compostela
  • Valencia, Spain
    • Incliva Biomedical Research Institute - Hospital Clinico Universitario Valencia
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, University Hospital Bern
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California USC Norris Comprehensive Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University Yale Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Lake Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Escalation; ALE.C04 single agent: Three planned doses of ALE.C04 and ALE.C04 in combination with pembrolizumab. Once a certain dose level of ALE.C04 is considered safe and well tolerated, the first cohort of patients receiving ALE.C04 at a lower dose level combined with pembrolizumab will be initiated	Drug: ALE.C04; Q3W; Drug: Pembrolizumab; 200mg Q3W; Other Names: Keytruda
Active Comparator: Phase 2 Randomized Combination part; ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy	Drug: ALE.C04; Q3W; Drug: Pembrolizumab; 200mg Q3W; Other Names: Keytruda
Experimental: Phase 1 Recommended Dose for Expansion; Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab	Drug: ALE.C04; Q3W; Drug: Pembrolizumab; 200mg Q3W; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicity (DLT)	Phase I dose escalation	21 days
Incidence and severity of adverse events (AEs), serious adverse events (SAEs)	Descriptive statistics will be used to summarize results	Up to 30 days after last dose - Approximately 4.5 years
Confirmed Objective Response Rate (ORR) by investigators assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 for Phase II	Up to 4.5 year
Confirmed Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment according to RECIST1.1	Time from start of study treatment to first documentation of objective progressive disease (PD) as per RECIST1.1 or to death due to any causes whichever come first during phase II	Up to 4.5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed ORR by investigators assessment according to RECIST1.1	Proportion of patients with confirmed CR or PR according to RECIST1.1	up to 4.5 year
Confirmed immune Objective Response Rate (iORR) by investigators assessment according to immune RECIST	Proportion of patients with confirmed immune CR or immune PR according to immune RECIST	up to 4.5 year
Disease Control Rate (DCR) as per investigator assessment according to RECIST1.1	Proportion of patients with CR, PR or Stable Disease (SD) according to RECIST1.1	up to 4.5 years
Immune Disease Control Rate (iDCR) as per investigator assessment according to immune RECIST	Proportion of patients with immune CR, immune PR or immune SD according to immune RECIST	up to 4.5 years
Duration Of Response (DOR)	The time from first documentation of objective response to the first documentation of PD per RECIST 1.1 or to death due to any cause, whichever comes first.	up to 4.5 years
Immune Duration Of Response (iDOR)	The time from first documentation of objective response to the first documentation of immune PD per immune RECIST or to death due to any cause, whichever comes first.	up to 4.5 years
Progression Free Survival (PFS) evaluated by investigators	The time from start of study treatment to first documentation of objective PD per RECIST1.1 following study therapy, or to death due to any cause, whichever comes first.	up to 4.5 years
Immune Progression Free Survival (iPFS) evaluated by investigators	The time from start of study treatment to first documentation of objective immune PD per immune RECIST following study therapy, or to death due to any cause, whichever comes first.	up to 4.5 years
Overall Survival (OS)	The time from start of study treatment to date of death due to any cause.	up to 4.5 years
Maximum serum concentration (Cmax) pharmacokinetics (PK) of ALE.C04	Maximum serum concentration (Cmax) will be derived by non-compartmental analysis and summarized by dose cohort	up to 4.5 years
Minimum serum concentration (Cmin) pharmacokinetics (PK) of ALE.C04	Minimum serum concentration will be derived by non-compartmental analysis and summarized by dose cohort	up to 4.5 years
Area under the concentration-time curve (AUC) pharmacokinetics (PK) of ALE.C04	Area under the concentration-time curve will be derived by non-compartmental analysis and summarized by dose cohort	up to 4.5 years
Maximum serum concentration (Cmax) Pharmacokinetics (PK) of pembrolizumab	Maximun Serum concentration (Cmax) by time point will be reported	up to 4.5 years
Minimum serum concentration (Cmin) Pharmacokinetics (PK) of pembrolizumab	Minimum serum concentration (Cmin) by time point will be reported	up to 4.5 years
Area under the concentration-time curve (AUC) Pharmacokinetics (PK) of pembrolizumab	Area under the concentration-time curve (AUC) by time point will be reported	up to 4.5 years
Immunogenicity of ALE.C04	To assess the presence of serum anti-drug antibodies (ADA) against ALE.C04	up to 4.5 years
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30	The C30 has 30 items in total. Among those items, 28 items are symptoms scales with score range from 1 to 4. A high score represents a high level of symptomatology. The 2 other items are global health status with score range of 1 to 7. A high score represents high quality of life.	Phase II combination part only - Up to 4.5 year
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Question Head and Neck module 43 (HN43)	The HN43 has 43 items of symptoms scale with score range of 1 to 4. A high score represents a high level of symptomatology.	Phase II combination part only - Up to 4.5 year

Collaborators and Investigators

• Sponsor: Alentis Therapeutics AG

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): February 12, 2025
• Study Completion (Actual): February 12, 2025

Study Registration Dates

• First Submitted: September 7, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Phase I/II; Anti-Claudin1; ALE.C04
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: ALE.C04.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No