Study of HRO761 Alone or in Combination in Cancer Patients With Specific DNA Alterations Called Microsatellite Instability or Mismatch Repair Deficiency.

The main purpose of the study is to evaluate the safety and tolerability of HRO761 and
identify the recommended dose(s), i.e., the optimal safe and active dose of HRO761 alone
or in combination with pembrolizumab or irinotecan that can be given to patients who have
cancers with specific molecular alterations called MSIhi (Microsatellite
Instability-high) or dMMR (Mismatch Repair Deficient) that might work best to treat these
specific cancer types and to understand how well HRO761 is able to treat those cancers. The new drug being tested in the study, HRO761, is an oral drug that acts on a protein
called Werner (WRN), which may contribute to cancer growth. By acting on WRN, HRO761 may
be able to stop the growth of the cancer.

This is the first time HRO761 is given to patients and the first time HRO761 is used in
combination with pembrolizumab or irinotecan.

Pembrolizumab and irinotecan are drugs approved in several countries and used as standard
treatment for certain types of cancer (e.g., colon cancer and small cell lung cancer).

This research study will consist of various treatment arms to investigate HRO761 as
single agent and in the combinations.

For HRO761 single agent, the research will be done in two parts. The first part is called
"dose escalation" and the second part is called "dose optimization". In the dose
escalation part, different groups of people will be given different doses of HRO761 to
understand how the body reacts to different doses of the drug and how well the drug acts
against the cancer. During the dose optimization part, the selected doses will be tested
in more patients until a recommended dose(s) is found.

The combinations of HRO761 with pembrolizumab or irinotecan also will be tested in a dose
escalation part to find the recommended doses of HRO761 in these combinations.

Once the recommended doses are determined, more people may be treated with HRO761 alone
or together with pembrolizumab or irinotecan to further assess the study treatment
effects against various types of MSIhi or dMMR cancers. This part is called dose
expansion.

For this research, a number of blood and tissue samples will be collected during the
study. Patients may be asked to come approximately 8 times to the clinic during the first
8 weeks and approximately every 2 or 4 weeks thereafter.

Patients will be in the study as long as their study doctor believes that they may be
benefiting from the study treatment, unless the patient decides to stop study treatment.