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

Overview

The primary objective is to evaluate major pathologic response after RiMO-301 with hypofractionated radiotherapy and a PD-1 inhibitor (pembrolizumab), as assessed by clinical response rate using iRECIST criteria; determine event-free survival for up to 12 months; and determine overall survival for up to 24 months. The secondary objectives include determining event-free survival for up to 12 months and overall survival for up to 24 months.

Detailed description

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.

Interventions

• Drug RiMO-301
  RiMO-301 will be dosed at 30% of the tumor volume on Day 0 prior to radiotherapy. The injection point will be as closed to half of the tumor depth as possible.
• Drug Pembrolizumab
  Pembrolizumab will be administered at 200 mg once every 3 weeks (Q3W) with the first dose on Day 0 +/- 1 day. Pembrolizumab will be given for a total of two cycles prior to surgery.
• Radiation Radiation
  Hypofractionated radiation will will be given within 1 day after RiMO-301 injection and will continue over a period of 5-15 days. Participants will be receive 5 fractions of radiation with a dose of 4-5 Gray per fraction.
• Procedure Surgical resection
  Surgical resection of the tumor will occur following neoadjuvant therapy.

Primary outcome measures

• Efficacy of RiMO-301 when used in combination with radiotherapy and pembrolizumab as defined by clinical response rate (i.e., percentage of participants whose tumors shrink). [Time frame: Treatment start until 12 months after the start of treatment]

Secondary outcome measures (7)

• Progression-free survival rate as defined by the number of patients whose disease progresses since the start of treatment [Time frame: Treatment start until 12 months after the start of treatment]
• Overall survival rate as defined by the number of deaths among participants [Time frame: Treatment start until 24 months after the start of treatment]
• Number of Grade 3 and Grade 4 toxicities experienced by participants as defined by CTCAE version 6 [Time frame: Treatment start until 5 weeks after the last dose of radiation therapy (that is, approximately 7 weeks after treatment start)]
• To assess the rate of Major Pathological Response (MPR) [Time frame: At surgical resection]
• To assess the rate of Pathological Complete Response (pCR) [Time frame: At surgical resection]
• To assess surgical outcomes through margin measurements at surgical resection [Time frame: At surgical resection]
• To evaluate the change in disease staging as assessed by the proportion of patients who have a reduction in the size or extent of tumor [Time frame: Pre-treatment until 12 months after the start of treatment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Illinois at Chicago — Chicago

Identifiers

NCT: NCT07732634 · 2026-0267

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗