Combination Study With Eftilagimod Alpha (a Soluble LAG-3 Fusion Protein) and Pembrolizumab in Patients With Recurrent or Metastatic HNSCC

Phase 2

Active, not recruiting

• Conditions: HNSCC
• Interventions: Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

• Registration Number: NCT04811027
• Lead Sponsor: Immutep S.A.S.

Brief Summary

Evaluate the safety and efficacy of eftilagimod alpha in combination with pembrolizumab against pembrolizumab alone in 1st line metastatic or recurrent HNSCC with programmed death-ligand 1 (PD-L1) positive (combined positive score \[CPS\] ≥1) tumors, and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumors.

Detailed Description

Up to 154 patients will be recruited in the TACTI-003 (Two ACTive Immunotherapies) Phase IIb study which will take place across several countries in Australia, Europe and United States of America in up to 35 experienced clinical sites. It will evaluate the safety and efficacy of eftilagimod alpha in combination with pembrolizumab against pembrolizumab alone in 1st line metastatic or recurrent HNSCC with PD-L1 positive (CPS ≥1) tumors, and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumors. Subjects in cohort A (CPS ≥1) will be randomized 1:1 to receive either "P+E": efti plus pembrolizumab or "P only": pembrolizumab alone. Subjects in cohort B (CPS \<1) will receive a combination of efti and pembrolizumab "P+E". Efti will be administered for up to 24 months using a 30 mg subcutaneous dosing every 2 or 3 weeks. Pembrolizumab will be administered for up to 24 months using a 400 mg intravenous (30 min) dosing every 6 weeks.

Study Timeline

• Study First Submitted: 2021-03-19
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-23
• Study Start: 2021-08-27
• Primary Completion: 2024-03-11
• Disposition First Posted: 2024-10-31
• Status Verified: 2025-02
• Disposition First Submitted: 2025-02-24
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-03
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

1. Histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx that is considered incurable by local therapies and to be treated in the first line palliative setting and who are PD-X naïve.
2. Availability of tissue for PD-L1 biomarker analysis from a core or excisional biopsy.
3. Availability of PD-L1 biomarker result by using the FDA approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx).
4. Availability of tissue for testing of human papillomavirus (HPV) status for oropharyngeal cancer (p16 expression testing).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Main

Exclusion Criteria

1. Disease is suitable for local therapy administered with curative intent.
2. Previously treated with ≥ 1 systemic regimen for recurrent and/or metastatic disease (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally or locoregionally advanced disease).
3. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including subjects with HNSCC of unknown primary, squamous cell carcinoma originating from skin, or non-squamous histologies (e.g. nasopharynx, salivary gland or mucosal melanoma).
4. Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locally or locoregionally advanced HNSCC, or requires chemotherapy based therapeutic regimen due to e.g., rapidly progressing disease or need of aggressive sympton control.
5. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
6. Has received prior chemotherapy, anti-cancer monoclonal antibody, major surgery, another systemic cancer therapy or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to cycle 1 day 1.
7. Known active central nervous system metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable: i.e. without evidence of progression documented by repeat imaging performed after therapy completed for CNS metastasis and with at least 4 weeks difference, clinically stable and without requirement for steroid treatment for at least 14 days prior to cycle 1 day 1.
8. Receives continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days prior to cycle 1 day 1. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
(CPS ≥1): pembrolizumab (KEYTRUDA®) + efti	eftilagimod alpha	eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).
(CPS ≥1): pembrolizumab (KEYTRUDA®) + efti	pembrolizumab (KEYTRUDA®)	eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).
(CPS ≥1): pembrolizumab (KEYTRUDA®)	pembrolizumab (KEYTRUDA®)	pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).
(CPS <1): pembrolizumab (KEYTRUDA®) + efti	pembrolizumab (KEYTRUDA®)	eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).
(CPS <1): pembrolizumab (KEYTRUDA®) + efti	eftilagimod alpha	eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to 24 months

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 24 months
Objective response rate (ORR) according to iRECIST	Up to 24 months
Time to and duration of responses according to iRECIST and RECIST 1.1	Up to 24 months
Disease control rate according to iRECIST and RECIST 1.1	Up to 24 months
Progression free survival (PFS) according to iRECIST and RECIST 1.1	Up to 24 months
Occurrence of anti-efti-specific antibodies	Up to 24 months
Frequency of (serious) adverse events	Up to 24 months
Severity of (serious) adverse events	Up to 24 months
Duration of (serious) adverse events	Up to 24 months
Quality of Life using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck (EORTC QLQ-H&N35)	Up to 24 months

Trial Locations

Locations (29)

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

University of Alabama at Birmingham (UAB) - O'Neal Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Oncology Consultants; 🇺🇸 Houston, Texas, United States

Macquarie University Hospital; 🇦🇺 Macquarie Park, New South Wales, Australia

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Herlev Hospital; 🇩🇰 Herlev, Denmark

Hospital de la Santa Creu i de Sant Pau; 🇪🇸 Barcelona, Spain

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

Nationales Centrum für Tumorerkrankungen Heidelberg; 🇩🇪 Heidelberg, Germany

Institut Català d'Oncologia - Hospital Universitari de Girona; 🇪🇸 Girona, Spain

Hospital Universitario Lucus Augusti; 🇪🇸 Lugo, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

START Madrid (Hospital Universitario Fundación Jiménez Díaz); 🇪🇸 Madrid, Spain

Hospital 12 Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Institute of Cancer Science - Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

University College London Hospitals NHS Foundation - The Harley Street Clinic; 🇬🇧 London, United Kingdom

Nottingham University Hospitals, NHS Trust; 🇬🇧 Nottingham, United Kingdom

AZ Sint-Jan Brugge; 🇧🇪 Brugge, Belgium

University Hospital Essen; 🇩🇪 Essen, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

AZ Nikolaas; 🇧🇪 Sint-Niklaas, Belgium

Antwerp University Hospital; 🇧🇪 Edegem, Belgium

The Oncology Institute "Prof Dr Ion Chiricuta" I.O.C.N.; 🇷🇴 Cluj-Napoca, Romania

Centre Hospitalier Universitaire (CHU) de Liege; 🇧🇪 Liège, Belgium

Universitätsklinikum Bonn; 🇩🇪 Bonn, NRW, Germany

Arensia Exploratory Medicine Llc; 🇺🇦 Kapitanivka, AL, Ukraine