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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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HNSCC

Intervention / Treatment
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* Drug: Eftilagimod alpha
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: 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). ECOG performance status 0-1. Main Exclusion Criteria: 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). 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). 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (CPS ≥1): Pembro + Efti<br>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<br>* APC activator, MHC II agonist, LAG-3 fusion protein<br>* Other names: Eftilagimod alfa;Drug: Pembrolizumab<br>* anti-PD-1 antibody<br>* Other names: MK-3475;|
| Active Comparator: (CPS ≥1): Pembro<br>Pembrolizumab: 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks). | Drug: Pembrolizumab<br>* anti-PD-1 antibody<br>* Other names: MK-3475;|
| Experimental: (CPS <1): Pembro + Efti<br>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<br>* APC activator, MHC II agonist, LAG-3 fusion protein<br>* Other names: Eftilagimod alfa;Drug: Pembrolizumab<br>* anti-PD-1 antibody<br>* Other names: MK-3475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) according to RECIST1.1 |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 EORTC QLQ-H&N35 |  | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HNSCC