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