Active not recruitingPHASE1INTERVENTIONAL

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

This study is looking into a new medicine called HRO761 for people with advanced cancers that have certain genetic changes (called MSI-high or dMMR). These changes mean the cancer cells can't repair their DNA properly. HRO761 is being tested on its own and with two other established cancer treatments, pembrolizumab or irinotecan. The main goals are to find out if HRO761 is safe, what the best dose is, and how well it works against these specific types of cancer. This is the first time HRO761 has been given to people. The study includes different stages to carefully increase the dose and then test it in more patients to learn more about its effects.

At a glance

Status

Active not recruiting

Phase

PHASE1

Sponsor

Novartis Pharmaceuticals

Enrolment target

123

Start

27 Jun 2023

Estimated completion

31 Aug 2027

MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal Cancers

What is this study about?

This research study is about a new drug called HRO761. It's designed for people with advanced cancers that have specific DNA problems, known as 'MSI-high' or 'dMMR'. These terms simply mean that the cancer cells have trouble fixing mistakes in their genetic code, which can make them grow and spread. HRO761 is taken by mouth and works by targeting a protein called Werner (WRN), which might help cancer grow. By affecting WRN, HRO761 could potentially slow down or stop cancer growth.

This is the very first time HRO761 is being given to people, and also the first time it’s being combined with two other well-known cancer drugs: pembrolizumab and irinotecan. Pembrolizumab and irinotecan are already approved and used to treat certain cancers in many countries. The study wants to see how safe HRO761 is, find the right dose, and understand how effective it is when used alone or with these other medicines for cancers with the MSI-high or dMMR features.

To figure this out, the study will have different groups of people. Initially, small groups will receive different doses of HRO761, either on its own or with pembrolizumab or irinotecan. This helps doctors learn how the body reacts to the drug and what dose is both safe and has the best chance of working. Once the best doses are found, more people will receive these doses to get a clearer picture of how well HRO761 treats a wider range of MSI-high or dMMR cancers.

Key takeaways

Tests a new drug (HRO761) for specific cancer types.
Aims to find safe doses and how well HRO761 works.
For cancers with 'MSI-high' or 'dMMR' DNA changes.
HRO761 given alone or with common cancer drugs.
First time HRO761 is used in people.

Who may be eligible?

This study is for adults generally between 18 and 100 years old. You might be able to join if you have certain advanced cancers that have either spread or can't be removed by surgery, and your cancer has the specific DNA changes called MSI-high or dMMR. You would also have already tried and not responded to, or couldn't tolerate, your previous standard cancer treatments.

There are some differences based on which group of the study you might join. For example, some groups require you to have already tried a certain type of immunotherapy. You also need to be reasonably fit and able to move around, and your cancer needs to be measurable so doctors can track any changes.

You would not be able to join if you have serious heart problems, significant eye issues, cancer in the brain or spinal cord, HIV, or active Hepatitis B, C, or Tuberculosis. Also, if you have severe issues with your digestive system that could prevent the study drug from being absorbed properly, or if you have had severe allergic reactions to any of the study drugs before, you wouldn't be able to participate. Your study doctor will consider all your health information to see if this study is right for you.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Is your cancer advanced, spread, or unable to be removed by surgery?
Does your cancer have MSI-high or dMMR DNA changes?
Have you already had and not responded to, or couldn't tolerate, previous standard cancer treatments?
Are you between 18 and 100 years old?
Are you generally well and active enough to do daily tasks (ECOG Performance Status of 1 or less)?

Answer every question to see your result.

What does participation involve?

If you join this study, you will be given HRO761, a new drug taken by mouth. Depending on which group you are in, you might also receive pembrolizumab or irinotecan. To monitor your health and how the treatment is working, you'll need to provide blood and tissue samples throughout the study. This helps the doctors understand the drug's effects and how your body is reacting.

During the first 8 weeks, you can expect to visit the clinic about 8 times. After this initial period, you'll likely have follow-up visits every 2 or 4 weeks. You will continue taking part in the study as long as your study doctor believes you are benefiting from the treatment and you wish to continue. You always have the right to stop participating at any time.

Potential risks and benefits

Participating in a study like this means you might be among the first to receive a new treatment that could potentially help your cancer, especially if other treatments haven't worked well. However, because HRO761 is new and has not been given to people before, there's a chance it might not work and it could have side effects that doctors don't fully know about yet. There may also be side effects from the other drugs if you receive a combination. The doctors will monitor you very closely for any unwanted effects to keep you as safe as possible. Remember, you can choose to leave the study at any time, for any reason, if you wish.

Locations (28)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

University of California LA
Verified postcode
Los Angeles, United States
UCSF
Verified postcode
San Francisco, United States
Dana Farber Cancer Institute
Verified postcode
Boston, United States
Memorial Sloan Kettering
Verified postcode
New York, United States
Columbia University Medical Ctr
Verified postcode
New York, United States
Univ of TX MD Anderson Cancer Cntr
Verified postcode
Houston, United States
Novartis Investigative Site
Verified postcode
Brussels, Belgium
Novartis Investigative Site
Verified postcode
Beijing, China
Novartis Investigative Site
Verified postcode
Guangzhou, China
Novartis Investigative Site
Verified postcode
Bordeaux, France
Novartis Investigative Site
Verified postcode
Marseille, France
Novartis Investigative Site
Verified postcode
Toulouse, France

Common questions

What do MSI-high and dMMR mean?

These are changes in your cancer's DNA that mean it has trouble fixing mistakes. The study focuses on treatments that might work best for cancers with these specific features.

Is HRO761 a common treatment?

No, HRO761 is a new drug being tested for the first time in people. It is not currently available outside of this study.

Will I definitely get HRO761?

Yes, everyone in this study will receive HRO761, either on its own or in combination with other approved cancer drugs like pembrolizumab or irinotecan.

How long will I be in the study?

You will stay in the study as long as your study doctor thinks the treatment is helping you, or until you decide you want to stop.

What are pembrolizumab and irinotecan?

These are established cancer medicines that are already approved and used to treat certain types of cancer in many countries.