Liver cancer

The study is currently in Phase 2 and is for patients with a diagnosis of unresectable metastatic uveal melanoma who have not been treated prior with Immune check point inhibitor therapy.

The purpose of this study is to measure the clinical benefits of the combination of RP2 and nivolumab as compared with the combination of nivolumab and ipilimumab in patients with metastatic uveal melanoma.

Key Elgibility Criteria

You may be eligible for this study if you meet the following conditions (note, full eligibility and exclusion criteria is available at clinicaltrials.gov):

• Are capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form.
• Patients who are 18 years of age or older at the time of signed informed consent.
• Patients with confirmed diagnosis of metastatic Uveal melanoma not amenable to surgical resection.
• Has at least 1 measurable and injectable tumor of ≥ 1 cm in longest diameter (≥ 1.5 cm in the shortest axis for a lymph node [LN]) that is amenable to serial RP2 injections.
• Must be willing to provide tumor biopsy samples.
• No exposure to immune checkpoint inhibitor (ICIs) since the time of first being diagnosed with uveal melanoma.
• LDH ≤ 2 × upper limit of normal (ULN).
• Has adequate hematologic, hepatic and renal function
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Life expectancy of > 6 months as estimated by the Investigator.

What to expect during the study

The study has three different phases. They are:

• Screening: Up to 28 days
• Treatment Period: Up to approximately 2 years
• Follow-up Period: Up to 3 years after treatment is completed

After the screening phase is completed, patients meeting all the inclusion criteria will be randomized into 1 of 2 treatment groups: RP2 + nivolumab or ipilimumab + nivolumab, which is an approved standard treatment for advanced melanoma.

Dosing of RP2 will start on Day 1 and will be administered directly into the tumor every 2 weeks for up to 8 cycles (approximately 4 months). After the first dose of RP2, dosing will be given with concurrent nivolumab infusion every 2 weeks up to 8 cycles and followed by either 2 weeks or 4 weeks dosing for up to an additional 20 months. Antitumor activity will be based on radiological and/or clinical evaluation and all patients will be assessed at Screening and once every 12 weeks.

IMPORTANT: Only your doctor can determine whether or not you are eligible to participate in this clinical study. Please note that if you decide to participate in the study, you can also choose to stop at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

This study is for patients with a diagnosis of advanced unresectable, recurrent, and/or metastatic hepatocellular carcinoma (HCC).

Key Elgibility Criteria

You may be eligible for this study if you meet the following conditions:

• Are at least 18 years old.
• Have had Child-Pugh A, determined within 14 days before first study treatment.
• Have at least 1 measurable tumor of ≥1 cm in longest diameter (or ≥1.5 cm shortest diameter for lymph nodes).
• Are capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form.
• Have no Child-Pugh B or C.
• Have no untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding.
• Have no histologic evidence of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma with HCC, or other rare HCC variants.
• Have no known acute or chronic hepatitis B or known acute or chronic hepatitis C virus.
• Have not received prior treatment with an oncolytic virus therapy.
• Have no prior organ transplantation including allogeneic stem-cell transplantation.

What to expect during the study

The study will consist of the following two treatment groups 1L Treatment Arm and 2L Treatment Arm.

1L Treatment Arm: locally advanced unresectable or metastatic HCC (no prior system therapy)

• RP3 administered once every three weeks for up to eight doses in combination with atezolizumab and bevacizumab.

2L Treatment Arm: recurrent or metastatic HCC progressed on one prior system treatment

• RP3 administered once every two weeks for the first four doses, followed by every three weeks for four doses in combination with atezolizumab and bevacizumab.

Patients will receive up to eight doses per course of RP3 in combination atezolizumab and bevacizumab.

Additional courses of RP3 may be administered every three weeks when applicable.

The study has different sections. They are:

Screening	Up to 28 days
Treatment Period	Up to 40 months
Follow-up Period	Up to 3 years

IMPORTANT: Only your doctor can determine whether or not you are eligible to participate in this clinical study. Please note that if you decide to participate in the study, you can also choose to stop at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.