A Study of ASP1012 in Adults With Solid Tumors

ASP1012 is a type of virus called an oncolytic virus which is used to treat some cancers.

ASP1012 was changed in a laboratory to infect and kill cancer cells, leaving healthy cells

alone. It also makes the cancer cells visible to the immune system which will fight the cancer

cells.

Before ASP1012 is available as a treatment, the researchers need to understand how it is

processed by and acts upon the body. This will help find a suitable dose for

future studies and check for potential medical problems from the treatment.

In this study, ASP1012 is being tested in humans for the first time. ASP1012 has already

been tested in the laboratory and in animals. This is the standard way new potential

treatments are developed.

People in this study will be adults whose tumor has either grown outside of the area where it

started (locally advanced) or it has spread to other parts of the body (metastatic). They will

receive ASP1012. Also, some people will receive ASP1012 with pembrolizumab, an

approved medicine.

There are 2 main aims of this study. The first is to learn if people with certain solid tumors

can tolerate different doses of ASP1012. The second is to find a suitable dose of ASP1012.

This study will be in 3 parts.

Part 1 is called Dose Escalation. People with locally advanced or metastatic tumors

can take part. They will have been previously treated with all available standard cancer

therapies. Different small groups of people will receive lower to higher doses of ASP1012.

For each dose, any medical problems will be recorded. This will help to find suitable

doses of ASP1012 to use in Parts 2 and 3 of the study. The first group will receive the lowest

dose of ASP1012. A medical expert panel will check the results from this group and decide

if the next group can receive a higher dose of ASP1012. The panel will do this for each

group until all groups have taken ASP1012 or until suitable doses have been selected for

Parts 2 and 3.

Part 2 is called Dose Expansion. 3 groups will take part: people with previously-treated melanoma (a

type of skin cancer) that have not responded to their treatment (refractory) or their cancer has

come back (relapsed), people with newly-diagnosed or untreated melanoma,

and people with previously-treated solid tumors. People with previously-treated melanoma will receive

ASP1012 at the dose worked out from Part 1. People with previously-treated

solid tumors will receive ASP1012 with pembrolizumab. The first few people will receive

ASP1012 at a lower dose than the dose worked out from Part 1, to check the safety of the

treatments being given together. If there are no safety issues: the next people in the solid

tumor group will receive ASP1012 at the dose worked out from Part 1, with pembrolizumab;

also people with untreated melanoma will receive ASP1012 at the dose worked out from Part

1, with pembrolizumab.

Part 3 is also a Dose Expansion for people with other specific cancers. These are stomach

cancer, ovarian cancer, or colorectal cancer. If people with certain tumors respond well in Parts 1 and

2 of the study, other people with this same type of tumor can also take part in Part 3.

For all parts of the study, ASP1012 will be given through a vein. This is called an infusion.

Each treatment cycle is 21 days long. People will start with 3 treatment cycles. People in the study may

receive extra treatment cycles, if they respond well to treatment. People

with melanoma who are receiving ASP1012 with pembrolizumab will not be offered the extra treatment

cycles. People can stop leave the study early if: they have medical problems from the treatment; their

cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come

back for treatment.

People will visit the clinic on certain days during their treatment. Some visits will be virtual

or by phone. During all clinic visits, the study doctors will check for any medical problems

from ASP1012. They will also check vital signs. Vital signs include temperature, pulse, breathing rate, the

amount of oxygen in the blood, and blood pressure. At some visits, other checks will also include a

medical examination, and an electrocardiogram (ECG) to check the heart rhythm, blood draws

and urine samples for testing. A tumor sample, if available, will be taken during the first

treatment cycle. People will have imaging scans and have blood draws for testing every 6

weeks during and after treatment. This will stop if they leave the study early.

People will visit the clinic within 7 days and 30 days after stopping treatment. At both visits,

the study doctors will check for any medical problems from ASP1012. Other checks will

include a medical examination, blood draws and urine samples for testing

and checking vital signs. An ECG will also be done at the 7-day visit. After the 30-day visit,

clinic staff will phone people in the study every 12 weeks to check the condition of their

cancer for up to 1 year.