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

NCT04811027 | Completed Phase 2 DMC FDA Drug

• 5 other identifiers: TACTI-0032021-000055-39KEYNOTE-C34MK-3475-C342024-510762-16-00
• Study Type: interventional
• Target: 171
• Locations: 9 countries
• Sites: 28

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.

Conditions

HNSCC

Keywords

HNSCC

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Up to 24 months

Secondary Outcomes (7)

• Overall survival (OS)

  Up to 24 months

• Objective response rate (ORR) according to iRECIST

  Up to 24 months

• 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

Study Arms (3)

(CPS ≥1): pembrolizumab (KEYTRUDA®) + efti

EXPERIMENTAL

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).

Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

(CPS ≥1): pembrolizumab (KEYTRUDA®)

ACTIVE COMPARATOR

pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).

Drug: pembrolizumab (KEYTRUDA®)

(CPS <1): pembrolizumab (KEYTRUDA®) + efti

EXPERIMENTAL

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).

Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

Interventions

eftilagimod alpha DRUG

APC activator, MHC II agonist, LAG-3 fusion protein

Also known as: IMP321, efti, eftilagimod alfa

(CPS <1): pembrolizumab (KEYTRUDA®) + efti; (CPS ≥1): pembrolizumab (KEYTRUDA®) + efti

pembrolizumab (KEYTRUDA®) DRUG

anti-PD-1 antibody

Also known as: MK-3475

(CPS <1): pembrolizumab (KEYTRUDA®) + efti; (CPS ≥1): pembrolizumab (KEYTRUDA®); (CPS ≥1): pembrolizumab (KEYTRUDA®) + efti

Eligibility Criteria

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

You may qualify if:

• 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.
• Availability of tissue for PD-L1 biomarker analysis from a core or excisional biopsy.
• Availability of PD-L1 biomarker result by using the FDA approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx).
• Availability of tissue for testing of human papillomavirus (HPV) status for oropharyngeal cancer (p16 expression testing).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

You may not qualify if:

• Disease is suitable for local therapy administered with curative intent.
• 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).
• 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.
• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Immutep S.A.S.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (28)

University of Alabama at Birmingham (UAB) - O'Neal Cancer Center

Birmingham, Alabama, 35249, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Oncology Consultants

Houston, Texas, 77030, United States

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Centre Hospitalier Universitaire (CHU) de Liege

Liège, 4000, Belgium

Location

AZ Nikolaas

Sint-Niklaas, 9100, Belgium

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2700, Denmark

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

Location

University Hospital Essen

Essen, 45147, Germany

Location

Nationales Centrum für Tumorerkrankungen Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

The Oncology Institute "Prof Dr Ion Chiricuta" I.O.C.N.

Cluj-Napoca, 400015, Romania

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i de Sant Pau

Barcelona, 08041, Spain

Location

Institut Català d'Oncologia - Hospital Universitari de Girona

Girona, 17007, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

START Madrid (Hospital Universitario Fundación Jiménez Díaz)

Madrid, 28040, Spain

Location

Hospital 12 Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Arensia Exploratory Medicine Llc

Kapitanivka, AL, 08112, Ukraine

Location

Institute of Cancer Science - Beatson West of Scotland Cancer Centre

Glasgow, 1053, United Kingdom

Location

University College London Hospitals NHS Foundation - The Harley Street Clinic

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals, NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

soluble LAG-3 protein, human; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 23, 2021
• Study Start: August 27, 2021
• Primary Completion: March 11, 2024
• Study Completion: November 5, 2025
• Last Updated: December 11, 2025

Record last verified: 2025-12

Locations

AU (1); DK (2); ES (8); US (3); UA (1); DE (4); BE (4); GB (4); RO (1)