Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma

KEY INCLUSION CRITERIA:

* ≥18 years of age (or as per national legal age of trial consent, whichever is higher) at date of signing the informed consent form (ICF).
* Histologically or cytologically confirmed r/m HNSCC, located in the oropharynx, considered incurable by local therapy and eligible for monotherapy with pembrolizumab.
* HPV16 positivity of r/m oropharyngeal HNSCC confirmed by designated central laboratory.

laboratory.

* PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.
* Primary tumor location in the oropharynx.
* At least 1 measurable lesion per RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
* Life expectancy of ≥3 months, as determined by Gustave Roussy Immuno (GRIm) score 0-1.

KEY Exclusion criteria:

HNSCC DISEASE

* Has disease that is suitable for local therapy with curative intent.
* Has progressive disease ≤6 months after completion of curatively intended concurrent chemoradiotherapy for locoregionally advanced r/m oropharyngeal HNSCC.
* Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any histology).
* Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator. PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS
* Has received prior palliative radiotherapy within 2 weeks of start of trial treatment or has a prior history of radiation pneumonitis.
* Any prior investigational or approved systemic antineoplastic drug or invasive medical device (including ICIs), either as monotherapy or as part of a combination regimen administered in the r/m HNSCC setting.
* Prior solid organ or tissue transplantation (except corneal transplant).
* Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT).
* Prior chimeric antigen receptor T (CAR-T) cell therapy.
* Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecules with similar mechanism of action) that engages T-cells.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.
* Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to trial treatment start.
* Prior administration with a therapeutic HPV16 vaccine.
* Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF-α) blockers for any concurrent condition.
* Chronic administration of systemic corticosteroids: prednisone \>10 mg daily (or dose equivalent).
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), including pembrolizumab in the locoregional setting.
* Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression.
* Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment. Accordingly, routine brain MRI at screening is not mandatory for all patients, only for those with previously treated but stable brain metastases.
* New (≤6 months), progressive and/or symptomatic brain metastases.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.