RiMO-HNC-NEO1: Phase 2 Study of RiMO-301 and Hypofractionated Radiotherapy With Pembrolizumab for the Neoadjuvant Treatment of Resectable, Locally Advanced Head-Neck Cancer

Inclusion Criteria:

* Diagnosis of head and neck cancer that requires surgical resection
* Must have at least one lesion that is clinically accessible to RiMO-301 injection and amenable to receiving hypofractionated radiotherapy
* The selected target lesions must be measurable on cross-sectional imaging, and repeated measurements at the same location should be achievable
* Target tumor not in the previously irradiated field or in the field irradiated at least six months prior to RiMO-301 injection, and with no complications from the prior radiation course
* Patients must have recovered from acute toxic effects (≤ grade 1 CTCAEv6) of previous cancer treatments prior to enrollment
* Patients with locally advanced, resectable head and neck cancer:

  * suitable to receive a PD-1 inhibitor (pembrolizumab) as a standard of care in the discretion of the treating physician or Principal Investigator
  * suitable to receive hypofractionated radiotherapy as a standard of care in the discretion of the treating physician or Principal Investigator
* Have adequate bone marrow reserve:

  * Absolute neutrophil count ≥1.5x109 cell/L
  * Platelet count ≥100x109 cell/L
  * Hemoglobin at least ≥9.0 g/dL unless confirmed by treating physician as not posing any increased harm to patient and approved by Sponsor (transfusion is allowed to achieve hemoglobin of ≥9.0 g/dL 14-days prior to dosing)
* Have adequate liver function:

  * Total serum bilirubin no more than 1.5x upper limit of normal (ULN)
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN or ≤5.0x ULN in case of documented hepatic metastasis
  * Alkaline phosphatase ≤5x ULN
* Have a life expectancy of at least 12 weeks (in the opinion of the investigator)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Females with childbearing potential should be using adequate contraceptive measures from the time of screening until 6 months after study discontinuation, should not be breastfeeding, and must have a negative pregnancy test prior to start of dosing
* Patients must sign a study-specific informed consent form prior to study entry.

Exclusion Criteria:

Diagnosis other than resectable, locally advanced head and neck cancers

* HPV associated head and neck cancer
* Nasopharynx head and neck cancer
* Have signs or symptoms of end-stage failure, major chronic illnesses other than cancer, or any severe concomitant conditions
* Symptomatic central nervous system metastases and/or carcinomatous meningitis
* Has received any approved or investigational anti-neoplastic agent or immunotherapy other than PD-1 inhibitors, pembrolizumab, within 4 weeks prior to RiMO-301 injection.
* Patients who are intolerant to pembrolizumab
* Active autoimmune disease that has required systemic treatment in the past 2 years
* Ongoing clinically significant infection at or near the incident lesion
* Major surgery over the target area (excluding placement of vascular access) ≤21 days from the beginning of the study drug or minor surgical procedures ≤7 days. No waiting is required following implantable port, enteral feeding tube, and catheter placement
* Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that would make the patient inappropriate for enrollment in this study
* Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial
* Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns
* Patients with a target lesion in the field that had complications from prior radiotherapy that are not amenable to repeat irradiation in the discretion of the treating physician or Principal Investigator
* Patients with lesions that have significant blood vessel involvement (such as carotid artery encasement) or other major structures