A phase 1 trial of RO7771950 (ZN-A-1041) enteric capsules or combination in participants with human epidermal growth factor receptor 2 (HER2)-positive advanced solid tumors

1. Why is this study needed?

HER2, also known as human epidermal growth factor receptor 2, is a protein involved in normal cell growth. It can be made in larger than normal amounts by some types of cancer cells, including breast cancer, and cause cancer cells to grow more quickly. ´HER2-positive’ or ‘HER2+’ means that cancer cells have more HER2 than normal. Solid tumors are cancer cells that grow in organ systems throughout the body, which are called advanced when they form a large tumor or may have started spreading in the body.

HER2-positive breast cancer makes up about 20% to 25% of all breast cancers, and up to half of the people with this cancer develop cancer in the brain. Treating tumors in the brain is still difficult with available medicines because these medicines can barely pass into the brain. Therefore, there is a strong need for new medicines that can target HER2 cancer and easily pass into the brain.

This study is testing a medicine called RO7771950 (previously called ZN-A-1041) alone or in combination with ado-trastuzumab emtansine (T-DM1), fam-trastuzumab deruxtecan-nxki (T-DXd), pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) or trastuzumab plus pertuzumab. It is being developed to treat HER2-positive advanced solid tumors.

RO7771950 is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved RO7771950 alone or in combination with T-DM1, T-DXd, Phesgo or trastuzumab plus pertuzumab for the treatment of HER2-positive advanced solid tumors.

This study aims to test how safe RO7771950 is at different doses, and how safe it is when given in combination with T-DM1, T-DXd, Phesgo, or trastuzumab plus pertuzumab. The study will also look at what happens to RO7771950 once it is in the body.

2. Who can take part in the study?

People (males and females) of 18 years of age with advanced solid tumors can take part in the study if their cancer is HER2-positive. People may not be able to take part in this study if  they have received any study medicine within 4 weeks before the first dose. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 4 weeks before the start of treatment.

Everyone who joins this study will be given RO7771950 as a capsule (to be swallowed) two times every day either alone or along with one of the following treatments, which are given once every 3 weeks:

• T-DXd given as a drip into a vein; or T-DM1 given as a drip into a vein; or Phesgo given as an injection under the skin or trastuzumab plus pertuzumab given as drips into a vein.

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants every  21 days. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have a follow-up visit 28 days after completing the study treatment, during which the study doctor will check on the participant’s well being. Total time of participation in the study will be about 1 year. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main result measured in the study is the number, type and seriousness of unwanted effects of RO7771950 given on its own or in combination with other study medicines. Other key results measured in the study include:

• How much RO7771950 is present in the blood and urine at different times during the treatment?

• How well RO7771950 alone or in combination with other study medicines shrinks the cancer or stops it from growing based on standard medical scans?

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study drugs:
Participants may have unwanted effects of the drugs used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Participants will be told about the known unwanted effects of RO7771950, T-DM1, T-DXd, Phesgo, and trastuzumab plus pertuzumab, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines.

Known unwanted effects of RO7771950 include increased liver proteins and pain in the head. Known unwanted effects of RO7771950 with T-DXd include low levels of a type of red blood cells that carry oxygen to the body, feeling less hungry than usual, a low level of potassium in the blood, and feeling dizzy or like you are passing out. Known unwanted effects of RO7771950 with Phesgo or trastuzumab plus pertuzumab include mild loose, watery and more frequent stools, wanting to throw up, throwing up, and feeling weak. Known unwanted effects of T-DM1 include wanting to throw up, feeling tired or weak, pain in the muscles or bones, bleeding, low levels of the blood cell fragments (called platelets) that help the blood to clot, and pain in the head.

RO7771950 will be given as a capsule to be swallowed. Participants will be told about any known unwanted effects of swallowing capsules. T-DM1, T-DXd, and trastuzumab plus pertuzumab will be given as a drip into a vein given slowly, and Phesgo will be given  by injection under the skin. Known unwanted effects of drips into a vein include discomfort, bruising and pain where the injection is given. Known unwanted effects of injections under the skin include redness, itchiness, swelling, warmth, pain, and tenderness/discomfort.

The study medicines may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.