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

RiMO-301 is administered intratumorally once prior to radiotherapy, with or without ultrasound/computed tomography (CT) guidance, at 30% of tumor volume(s). Radiotherapy (RT) is given starting within 1 day after RiMO-301 injection for 5 fractions of (4-5) Gray per fraction over a period of 5-15 days. PD-1 inhibitor pembrolizumab will be administered via 30-minute intravenous infusion, respectively, 200 mg once every three weeks (Q3W) with the first dose on the same day as RiMO-301 injection (+/- 1 day) for two cycles. Assessment of response will be clinically confirmed with CT imaging studies performed 5 weeks after the last radiation and pathology evaluation of the resected tumor. Event-free survival will be clinically evaluated every three months up to 12 months, CT imaging studies will be performed every 6 months after surgery up to 12 months after surgery, and overall survival will be clinically evaluated up to two years.

Age

18–any

Sex

ALL

Healthy volunteers

Not accepted

You may be eligible if

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.

You may not be if

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

What this study is about