Phase I Study of RiMO-301 With Radiation in Advanced Tumors

Primary Objectives:

• The primary objective is to determine the maximum tolerated dose (MTD) of RiMO-301 as determined by toxicity observed in patients treated with palliative radiation doses

Secondary Objectives:

• To determine clinical response after RiMO-301 and radiotherapy as assessed by clinical response rate using clinical evaluation, imaging and/or symptom relief
• To characterize adverse events of RiMO-301 in patients with advanced cancers
• To evaluate the pharmacokinetics (PK) of RiMO-301 with radiation

The target population is patients with clinically accessible lesions for intratumoral injection. Up to 3 dose levels (5%, 10%, and 15% of the total baseline tumor volume, respectively) will be tested in a 3 + 3 dose escalation study design. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intratumor injection of RiMO-301 to 30 days after the completion of radiation treatment:

• Grade 4 or greater treatment related hematologic or dermatologic toxicity
• Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity (excluding nausea, vomiting or diarrhea without maximal medical intervention)

Inclusion criteria

• Diagnosis of advanced or metastatic cancer not amenable to curative therapy
• Lesion that is amenable to palliative radiotherapy
• Lesion that is technically feasible to irradiation and accessible for direct intratumoral injection
• Target tumor in region not in previously irradiated field
• Patient must have recovered from acute toxic effects (≤ grade 1) of previous cancer treatments prior to enrollment
• Age >18 years
• Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion
• Females with child bearing age should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to the start of dosing
• Patients must sign a study-specific informed consent form prior to study entry

Exclusion criteria

• Patients with a histological diagnosis of lymphomas and/or leukemias
• Patients may not have received chemotherapy, targeted therapies, biologic response modifiers and/or hormonal therapy within the last 14 days
• 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
• 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
• Patients with a target lesion located in a previously irradiated field