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TACTI-003: Combination Study With Eftilagimod Alpha (a Soluble LAG-3 Fusion Protein) and Pembrolizumab in Patients With Recurrent or Metastatic HNSCC

Sponsor
Immutep S.A.S. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04811027
Collaborator
Merck Sharp & Dohme LLC (Industry)
154
Enrollment
24
Locations
3
Arms
42.1
Anticipated Duration (Months)
6.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 PD-L1 positive (CPS ≥1) tumors, and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumors.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 s.c. dosing every 2 or 3 weeks. Pembrolizumab will be administered for up to 24 months using a 400mg i.v. (30 min) dosing every 6 weeks.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
TACTI-003 (Two ACTive Immunotherapeutics): A Multicenter, Open Label, Randomized, Phase II Trial to Investigate a Soluble LAG-3 Fusion Protein, Eftilagimod Alpha (Efti; IMP321) in Combination With Pembrolizumab (PD-1 Antagonist) for First Line Treatment of Subjects With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)
Actual Study Start Date :
Aug 27, 2021
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Mar 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: (CPS ≥1): Pembro + Efti

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

Drug: Eftilagimod alpha
APC activator, MHC II agonist, LAG-3 fusion protein
Other Names:
  • IMP321
  • Efti

    • Drug: Pembrolizumab
    anti-PD-1 antibody
    Other Names:
  • Keytruda
  • MK-3475

    		•
    Active Comparator: (CPS ≥1): Pembro

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

    Drug: Pembrolizumab
    anti-PD-1 antibody
    Other Names:
  • Keytruda
  • MK-3475

    		•
    Experimental: (CPS <1): Pembro + Efti

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

    Drug: Eftilagimod alpha
    APC activator, MHC II agonist, LAG-3 fusion protein
    Other Names:
  • IMP321
  • Efti

    • Drug: Pembrolizumab
    anti-PD-1 antibody
    Other Names:
  • Keytruda
  • MK-3475

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective response rate (ORR) according to RECIST1.1 [Up to 24 months]

    Secondary Outcome Measures

    1. Overall survival (OS) [Up to 24 months]

    2. Objective response rate (ORR) according to iRECIST [Up to 24 months]

    3. Time to and duration of responses according to iRECIST and RECIST 1.1 [Up to 24 months]

    4. Disease control rate according to iRECIST and RECIST 1.1 [Up to 24 months]

    5. Progression free survival (PFS) according to iRECIST and RECIST 1.1 [Up to 24 months]

    6. Occurrence of anti-efti-specific antibodies [Up to 24 months]

    7. Frequency of (serious) adverse events [Up to 24 months]

    8. Severity of (serious) adverse events [Up to 24 months]

    9. Duration of (serious) adverse events [Up to 24 months]

    10. Quality of Life using EORTC QLQ-H&N35 [Up to 24 months]

    Other Outcome Measures

    1. PD-L1 expression [At Screening: three weeks prior to cycle 1 day 1]

    2. Circulating level of TH1 biomarker [Up to 24 months]

    3. Correlation of biomarkers or other characteristics with any efficacy or safety endpoint [Up to 24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Main 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. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham (UAB) - O'Neal Cancer Center Birmingham Alabama United States 35249
    2 Washington University School of Medicine Saint Louis Missouri United States 63110
    3 Oncology Consultants Houston Texas United States 77030
    4 Border Medical Oncology Research Unit East Albury New South Wales Australia 2640
    5 Macquarie University Hospital Macquarie Park New South Wales Australia 2109
    6 Chris O'Brian Lifehouse Camperdown Australia NSW 2050
    7 AZ Sint-Jan Brugge Brugge Belgium 8000
    8 Antwerp University Hospital Edegem Belgium 2650
    9 Centre Hospitalier Universitaire (CHU) de Liege Liège Belgium 4000
    10 AZ Nikolaas Sint-Niklaas Belgium 9100
    11 Rigshospitalet Copenhagen Denmark 2100
    12 Herlev Hospital Herlev Denmark 2700
    13 Odense University Hospital Odense Denmark 5000
    14 Vall d'Hebron Institute of Oncology (VHIO) Barcelona Spain 08035
    15 Hospital de la Santa Creu i de Sant Pau Barcelona Spain 08041
    16 Institut Català d'Oncologia - Hospital Universitari de Girona Girona Spain 17007
    17 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    18 START Madrid (Hospital Universitario Fundación Jiménez Díaz) Madrid Spain 28040
    19 Hospital Universitario Miguel Servet Zaragoza Spain 50009
    20 Arensia Exploratory Medicine Llc Kapitanivka AL Ukraine 08112
    21 Institute of Cancer Science - Beatson West of Scotland Cancer Centre Glasgow United Kingdom 1053
    22 University College London Hospitals NHS Foundation - The Harley Street Clinic London United Kingdom NW1 2PG
    23 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
    24 Nottingham University Hospitals, NHS Trust Nottingham United Kingdom NG5 1PB

    Sponsors and Collaborators

    • Immutep S.A.S.
    • Merck Sharp & Dohme LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Immutep S.A.S.
    ClinicalTrials.gov Identifier:
    NCT04811027
    Other Study ID Numbers:
    • TACTI-003
    • Keynote- PNC-34
    First Posted:
    Mar 23, 2021
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Immutep S.A.S.
    HNSCC
    Additional relevant MeSH terms:
    Squamous Cell Carcinoma of Head and Neck
    Pembrolizumab

    Study Results

    No Results Posted as of Aug 1, 2022