Study of RiMO-301 and Radiotherapy With PD-1 Inhibitor for the Treatment of Head-Neck Cancer

This is a prospective, open-label, single arm, non-randomized study of RiMO-301 with hypofractionated radiation and a PD-1 Inhibitor in patients with unresectable, recurrent or metastatic head-neck cancer.

Primary Objectives:

* To determine the tolerability of RiMO-301 with hypofractionated X-ray radiotherapy and a PD-1 inhibitor (pembrolizumab or nivolumab) in patients with unresectable, recurrent or metastatic head-neck cancer
* To determine the efficacy of RiMO-301 with hypofractionated X-ray radiotherapy and a PD-1 inhibitor (pembrolizumab or nivolumab)

Secondary Objectives:

* To evaluate progression-free survival for up to 12 months
* To determine overall survival for up to 24 months
* To assess patient quality of life

The target population is patients with unresectable, recurrent or metastatic head-neck cancer which is clinically accessible to intratumoral injection.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of head-neck cancer that requires palliative radiotherapy
* Patients with unresectable, recurrent or metastatic HNSCC, regardless if the patients have progressed on or are intolerant to platinum-based chemotherapy prior to study enrollment or if the patients are receiving pembrolizumab in the first line:

  * receiving a PD-1 inhibitor (pembrolizumab or nivolumab) as a standard of care, or
  * suitable to receive a PD-1 inhibitor (pembrolizumab or nivolumab) as a standard of care in the discretion of the treating physician or Principal Investigator
* Must have at least 1 target lesion that is clinically accessible to RiMO-301 injection and amenable to receive RT regimens specified in this protocol
* 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
* RiMO-301 injection to multiple lesions (≤ 5 in total) in a single patient is allowed as long as the total tumor volume does not exceed 250 cm3
* Patient must have recovered from acute toxic effects (≤ grade 1 CTCAEv5) of previous cancer treatments prior to enrollment
* Have adequate bone marrow reserve and adequate liver function
* Have a life expectancy of at least 12 weeks
* ECOG score of 0-2
* Age 18 years or older

Exclusion Criteria:

* Have signs or symptoms of end organ failure, major chronic illnesses other than cancer, or any severe concomitant conditions
* Symptomatic central nervous system metastases and/or carcinomatous meningitis
* 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 beginning of the study drug or minor surgical procedures ≤7 days. No waiting is required following implantable port, enteral feeding tube and catheter placement
* Has received any approved or investigational anti-neoplastic agent or immunotherapy other than PD-1 inhibitors (pembrolizumab or nivolumab) within 4 weeks prior to RiMO-301 injection
* Patients with lesions which have significant blood vessel involvement (such as carotid artery encasement) or other major structures