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

Phase 2TerminatedNCT06054477

Alentis Therapeutics AG21 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Cancer Head and Neck Squamous Cell Carcinoma

Interventions

ALE.C04DRUG

Q3W

PembrolizumabDRUG

200mg Q3W

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (22)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Outcomes

Primary Outcomes

Incidence of Dose Limiting Toxicity (DLT)

Phase I dose escalation

Time frame: 21 days

Incidence and severity of adverse events (AEs), serious adverse events (SAEs)

Descriptive statistics will be used to summarize results

Time frame: 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

Time frame: 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

Time frame: Up to 4.5 year

Secondary Outcomes

Confirmed ORR by investigators assessment according to RECIST1.1

Proportion of patients with confirmed CR or PR according to RECIST1.1

Time frame: 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

Time frame: up to 4.5 year

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

Data from ClinicalTrials.gov

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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

...and 12 more locations

Proportion of patients with CR, PR or Stable Disease (SD) according to RECIST1.1

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: up to 4.5 years

Overall Survival (OS)

The time from start of study treatment to date of death due to any cause.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: up to 4.5 years

Maximum serum concentration (Cmax) Pharmacokinetics (PK) of pembrolizumab

Maximun Serum concentration (Cmax) by time point will be reported

Time frame: up to 4.5 years

Minimum serum concentration (Cmin) Pharmacokinetics (PK) of pembrolizumab

Minimum serum concentration (Cmin) by time point will be reported

Time frame: 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

Time frame: up to 4.5 years

Immunogenicity of ALE.C04

To assess the presence of serum anti-drug antibodies (ADA) against ALE.C04

Time frame: 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.

Time frame: 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.

Time frame: Phase II combination part only - Up to 4.5 year