Summary

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

Eligibility

1. Participants in Parts 1 and 2 must have histologically, or cytologically, confirmed diagnosis of locally advanced or metastatic solid tumor(s).
2. Dose Escalation (Part 1) - all previously treated participants with solid tumor types
3. Dose Expansion (Part 2)
4. Participants with previously treated cutaneous melanoma, that is, anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) alone or in combination with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor. Participants with BRAF-mutant melanoma must have received a v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor as monotherapy or in combination with other targeted agents (for example, murine embryonic fibroblasts (MEK) inhibitors).
5. Participants with previously treated solid tumors,
6. Participants with stage IIIB to IIID or oligometastatic resectable stage IV, treatment-naïve melanoma that are amenable to resection. Note: Participants with acral lentiginous melanoma will be excluded.
7. Participants in Part 3 (Dose Expansion) must have histologically, or cytologically confirmed diagnosis of either:
8. Previously treated (at least 1 line of prior therapy) gastric cancer (including gastroesophageal junction cancer [type 2 and 3 only]). Prior lines of therapy may include combination chemotherapy such as FOLFOX based regimen containing 5-flurouracil, leucovorin and oxaliplatin, targeted therapies against human epidermal growth factor receptor 2 (HER2+) tumors and checkpoint inhibitors.
9. Stage II to IV CRC in complete remission with no measurable disease as defined by RECIST v1.1 following surgical resection and adjuvant therapy with circulating tumor deoxyribonucleic acid (ctDNA) detectable by local testing; the ctDNA positivity will be confirmed during the trial by centralized testing Note: Participants with Stage IV CRC are limited to those with oligometastatic disease in liver. Participants with CRC must have received and completed standard of care and adjuvant therapies which may include fluoropyrimidine, oxaliplatin, bevacizumab, and irinotecan-based chemotherapy and surgery.
10. Stage II to IV ovarian cancer including breast cancer gene mutations in complete remission with no measurable disease as defined by RECIST v1.1 following surgical resection and adjuvant therapy with CA-125 concentration exceeding 2 times of normal level (> 70 units per milliliter [U/mL]) as measured by local testing. Participants with ovarian cancer must have received standard of care and adjuvant therapies which may include platinum-based chemotherapy and/or poly-ADP ribose polymerase (PARP) inhibitors.
11. Other solid tumor type (when identified), for example, a tumor type in which antitumor activity or biomarker response is observed in Parts 1 or 2 or additional tumor types of interest.
12. Participant has measurable disease as determined by RECIST v1.1, except for participants with CRC and ovarian cancer enrolled in Part 3. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
13. Participant has progressed, relapsed or discontinued for toxicity during or after the last systemic anti-neoplastic therapy and is unlikely to achieve clinical benefit from standard of care therapies per investigator, except for Part 2 participants with treatment-naïve melanoma and Part 3 (participants with CRC and ovarian cancer). There is no limit to the number of prior anti-neoplastic therapies received.
14. Participant has a predicted life expectancy = 12 weeks.
15. Participant has at least 1 site of disease suitable for biopsy (except for Part 3 [participants with CRC and ovarian cancer]) and is willing and able to undergo required tumor biopsies according to the treating institution's guidelines at screening and during study treatment. Bone biopsies are not acceptable.
16. Participant has an ECOG performance status of 0 or 1.
17. Female participant:
18. Is not pregnant and at least 1 of the following conditions apply:
19. Not a woman of child bearing potential (WOCBP)
20. WOCBP who has a negative urine or serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent throughout the treatment period and for at least 180 days after the final ASP1012 administration.
21. Must not be breastfeeding or lactating starting at screening and throughout the treatment period and 180 days after the final ASP1012 administration.
22. Must not donate ova starting at first administration of study intervention and throughout the treatment period and for 180 days after the final ASP1012 administration.
23. Male participant:
24. Must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 180 days after the final ASP1012 administration.
25. Must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 180 days after the final ASP1012 administration.
26. Must not donate sperm during the treatment period and for 180 days after the final ASP1012 administration.
27. Participant must be willing and able to comply with the study requirements including prohibited concomitant medication restrictions.
28. Participant agrees not to participate in another interventional study while receiving ASP1012 in the present study/participating in the present study.

Treatment Sites in Georgia