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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06054477
• Other study ID #: ALE.C04.01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 30, 2023
• Est. completion date: February 2028

Study information

• Verified date: August 2023
• Source: Alentis Therapeutics AG
• Contact: Luigi Manenti, MD
• Phone: 41782304288
• Email: ale.c04.01[@]alentis.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: February 2028
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• ALE.C04
Q3W
• Pembrolizumab
200mg Q3W

Locations

Country	Name	City	State
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto	Ontario
Hong Kong	Prince Of Wales Hospital	Hong Kong
Italy	Candiolo cancer Center,FPO IRCCS	Candiolo	Piedmont
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori Di Milano	Milan
Singapore	National Cancer Centre Singapore	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
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
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Washington University School of Medicine	Lake Saint Louis	Missouri
United States	University of Southern California USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Yale University Yale Cancer Center	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Alentis Therapeutics AG

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Italy,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicity (DLT)	Phase I dose escalation	21 days
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)	The time from start of study treatment to date of death due to any cause.	up to 4.5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximum serum concentration (Cmax) Pharmacokinetics (PK) of pembrolizumab	Maximun Serum concentration (Cmax) by time point will be reported	up to 4.5 years
Secondary	Minimum serum concentration (Cmin) Pharmacokinetics (PK) of pembrolizumab	Minimum serum concentration (Cmin) by time point will be reported	up to 4.5 years
Secondary	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
Secondary	Immunogenicity of ALE.C04	To assess the presence of serum anti-drug antibodies (ADA) against ALE.C04	up to 4.5 years
Secondary	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
Secondary	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