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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Лучевая терапия 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.
• Процедура Surgical resection
  Surgical resection of the tumor will occur following neoadjuvant therapy.

Первичные конечные точки

• 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). [Срок оценки: Treatment start until 12 months after the start of treatment]

Вторичные конечные точки (7)

• Progression-free survival rate as defined by the number of patients whose disease progresses since the start of treatment [Срок оценки: Treatment start until 12 months after the start of treatment]
• Overall survival rate as defined by the number of deaths among participants [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: At surgical resection]
• To assess the rate of Pathological Complete Response (pCR) [Срок оценки: At surgical resection]
• To assess surgical outcomes through margin measurements at surgical resection [Срок оценки: 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 [Срок оценки: Pre-treatment until 12 months after the start of treatment]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Illinois at Chicago — Chicago

Идентификаторы

NCT: NCT07732634 · 2026-0267

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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