Clinical trial NCT04811027: Combination Study With Eftilagimod Alpha (a Soluble LAG-3 Fusion Protein) and Pembrolizumab in Patients With Recurrent or Metastatic HNSCC
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HNSCC
Keywords: HNSCC
Lead sponsor: Immutep S.A.S.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-03-23
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. 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.

Primary outcomes:
measure: Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 24 months
measure: Objective response rate (ORR) according to iRECIST
timeFrame: Up to 24 months
measure: Time to and duration of responses according to iRECIST and RECIST 1.1
timeFrame: Up to 24 months
measure: Disease control rate according to iRECIST and RECIST 1.1
timeFrame: Up to 24 months
measure: Progression free survival (PFS) according to iRECIST and RECIST 1.1
timeFrame: Up to 24 months
measure: Occurrence of anti-efti-specific antibodies
timeFrame: Up to 24 months
measure: Frequency of (serious) adverse events
timeFrame: Up to 24 months
measure: Severity of (serious) adverse events
timeFrame: Up to 24 months
measure: Duration of (serious) adverse events
timeFrame: Up to 24 months
measure: Quality of Life using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck (EORTC QLQ-H&N35)
timeFrame: Up to 24 months
Other outcomes:
measure: PD-L1 expression
timeFrame: At Screening: three weeks prior to cycle 1 day 1
measure: Circulating level of TH1 biomarker
timeFrame: Up to 24 months
measure: Correlation of biomarkers or other characteristics with any efficacy or safety endpoint
timeFrame: Up to 24 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) - O'Neal Cancer Center
state: Alabama
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) de Liege
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: NRW
city: Essen
country: Germany
facility: University Hospital Essen
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen Heidelberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Cluj-Napoca
country: Romania
facility: The Oncology Institute "Prof Dr Ion Chiricuta" I.O.C.N.
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Girona
country: Spain
facility: Institut Català d'Oncologia - Hospital Universitari de Girona
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: START Madrid (Hospital Universitario Fundación Jiménez Díaz)
city: Madrid
country: Spain
facility: Hospital 12 Octubre
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kapitanivka
country: Ukraine
facility: Arensia Exploratory Medicine Llc
state: AL
city: Glasgow
country: United Kingdom
facility: Institute of Cancer Science - Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation - The Harley Street Clinic
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals, NHS Trust
Study officials:
References: