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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 1b/2a Study of RiMO-301 and Hypofractionated Radiotherapy With A PD-1 Inhibitor for the Treatment of Unresectable, Recurrent or Metastatic Head-Neck Cancer

Conditions
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Intratumoral Injection, Head Neck Cancer

Intervention / Treatment
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* Drug: RiMO-301


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RiMO-301<br>Intratumoral injection of RiMO-301 followed by pembrolizumab or nivolumab followed by hypofractionated radiation | Drug: RiMO-301<br>* A single dose of RiMO-301 will be administered via an intratumoral injection. PD-1 inhibitor (pembrolizumab or nivolumab) will be administered via a 30-minute intravenous infusion until disease progression or unacceptable toxicity. Patients will receive hypofractionated radiation in 5 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Recommended Dose | • The dose limiting toxicities of RiMO-301 with hypofractionated X-ray radiotherapy and a PD-1 inhibitor, as assessed by CTCAEv5, will not be observed in 33% or more patients | 6 weeks | 
| Evaluation of Anti-Tumor Response | • To determine the objective response rate: complete or partial response, as defined by RECIST and itRECIST | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Progression-Free Survival | Time from enrollment to local-regional recurrence, local-regional progression, distant progression or death from any cause, whichever occurs first | 12 months | 
| Evaluation of Overall Survival | Time from enrollment to death from any cause | 24 months |