TACTI-003: This Phase II trial is evaluating how safe and effective a targeted therapy (eftilagimod alpha) is when combined with immunotherapy (pembrolizumab) compared to pembrolizumab alone in people with metastatic or recurrent squamous cell carcinoma of the head and neckTACTI-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)

Exclusion

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.