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

NCT06054477 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ALE.C04.01
• Study Type: interventional
• Target: 21
• Locations: 8 countries
• Sites: 22

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.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

Immunotherapy; Anti-Claudin1; ALE.C04; Phase I/II

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (18)

• Confirmed ORR by investigators assessment according to RECIST1.1

  up to 4.5 year

• Confirmed immune Objective Response Rate (iORR) by investigators assessment according to immune RECIST

  up to 4.5 year

• Disease Control Rate (DCR) as per investigator assessment according to RECIST1.1

  up to 4.5 years

• Immune Disease Control Rate (iDCR) as per investigator assessment according to immune RECIST

  up to 4.5 years

• Duration Of Response (DOR)

  up to 4.5 years

Study Arms (3)

Phase 1 Dose Escalation

EXPERIMENTAL

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; Drug: Pembrolizumab

Phase 1 Recommended Dose for Expansion

EXPERIMENTAL

Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab

Drug: ALE.C04; Drug: Pembrolizumab

Phase 2 Randomized Combination part

ACTIVE COMPARATOR

ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy

Drug: ALE.C04; Drug: Pembrolizumab

Interventions

ALE.C04 DRUG

Q3W

Phase 1 Dose Escalation; Phase 1 Recommended Dose for Expansion; Phase 2 Randomized Combination part

Pembrolizumab DRUG

200mg Q3W

Also known as: Keytruda

Phase 1 Dose Escalation; Phase 1 Recommended Dose for Expansion; Phase 2 Randomized Combination part

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consents
• Be 18 years of age on day of signing informed consent.
• Have histologically or cytologically confirmed Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) that is considered incurable by local therapies.
• 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.
• Have measurable disease based on RECIST 1.1 as determined by the site.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer

You may not qualify if:

• Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC (Phase II randomized combination part only).
• 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.
• 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.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• 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.
• 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.
• Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1 or anti-PD-L2 (Phase II randomized combination part only).

Sponsors & Collaborators

• Alentis Therapeutics AG: lead

Study Sites (22)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Southern California USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Yale University Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

Lake Saint Louis, Missouri, 63110, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre

Bordeaux, 33075, France

Location

Oncopole Claudius Regaud, Iuct-Oncopole

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Prince Of Wales Hospital

Hong Kong, Hong Kong

Location

Candiolo cancer Center,FPO IRCCS

Candiolo, Piedmont, 10060, Italy

Location

Fondazione Irccs Istituto Nazionale Dei Tumori Di Milano

Milan, Italy

Location

Istituto Europeo Di Oncologia S.R.L.

Milan, 20141, Italy

Location

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, Spain

Location

Incliva Biomedical Research Institute - Hospital Clinico Universitario Valencia

Valencia, Spain

Location

Inselspital, University Hospital Bern

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 26, 2023
• Study Start: October 30, 2023
• Primary Completion: February 12, 2025
• Study Completion: February 12, 2025
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

FR (3); SG (2); IT (3); US (7); ES (4); CA (1); CH (1); HK (1)