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

Phase 1

Terminated

• Conditions: Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: ALE.C04; Drug: Pembrolizumab

• Registration Number: NCT06054477
• Lead Sponsor: Alentis Therapeutics AG

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 as monotherapy and to assess anti-tumor activity of ALE.C04 monotherapy and 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 both ALE.C04 monotherapy and in combination with pembrolizumab. The phase II comprises a 1:1 randomized 2 arms assessing 2 dose levels of ALE.C04 as monotherapy and a 1:1 randomized 2 arms assessing ALE.C04 and pembrolizumab given in combination versus pembrolizumab monotherapy

Study Timeline

• Study First Submitted: 2023-09-07
• Study First Submitted QC: 2023-09-19
• Study First Posted: 2023-09-26
• Study Start: 2023-10-30
• Status Verified: 2025-02
• Primary Completion: 2025-02-12
• Study Completion: 2025-02-12
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1 Dose Escalation	ALE.C04	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
Phase 1 Dose Escalation	Pembrolizumab	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
Phase 1 Recommended Dose for Expansion	ALE.C04	Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab
Phase 1 Recommended Dose for Expansion	Pembrolizumab	Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab
Phase 2 Randomized Combination part	ALE.C04	ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy
Phase 2 Randomized Combination part	Pembrolizumab	ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy

Primary Outcome Measures

Name	Time	Method
Incidence of Dose Limiting Toxicity (DLT)	21 days	Phase I dose escalation
Confirmed Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment according to RECIST1.1	Up to 4.5 year	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
Incidence and severity of adverse events (AEs), serious adverse events (SAEs)	Up to 30 days after last dose - Approximately 4.5 years	Descriptive statistics will be used to summarize results
Confirmed Objective Response Rate (ORR) by investigators assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to 4.5 year	Proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 for Phase II

Secondary Outcome Measures

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

Trial Locations

Locations (22)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

University of Southern California USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Yale University Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Washington University School of Medicine; 🇺🇸 Lake Saint Louis, Missouri, United States

Gabrail Cancer Center Research; 🇺🇸 Canton, Ohio, United States

University Health Network, Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre; 🇫🇷 Bordeaux, France

Oncopole Claudius Regaud, Iuct-Oncopole; 🇫🇷 Toulouse, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Prince Of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong

Candiolo cancer Center,FPO IRCCS; 🇮🇹 Candiolo, Piedmont, Italy

Istituto Europeo Di Oncologia S.R.L.; 🇮🇹 Milano, Italy

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore

Tan Tock Seng Hospital; 🇸🇬 Singapore, Singapore

Fondazione Irccs Istituto Nazionale Dei Tumori Di Milano; 🇮🇹 Milan, Italy

Vall d'Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

MD Anderson Cancer Center; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Incliva Biomedical Research Institute - Hospital Clinico Universitario Valencia; 🇪🇸 Valencia, Spain

Inselspital, University Hospital Bern; 🇨🇭 Bern, Switzerland