A study to assess the safety, tolerability and effect of RO7673396 when used alone as well as with other cancer medications in participants with advanced solid tumors

1. Why is this study needed? 

Solid tumors are caused by uncontrolled growth of cells. These can occur in various organs and tissues throughout the body. Advanced solid tumors are cancers that have spread to other parts of the body. Changes (mutations) in a gene called RAS cause cells to grow uncontrollably, leading to cancer. RAS mutations make cancers harder to treat as they can resist many therapies. Therefore, there is a need to find new treatments.

This study is testing the medicine RO7673396 alone and in combination with another cancer medicine called tambotatug pelitecan (Tam-Peli). RO7673396 is being developed to treat solid tumors, which have spread in the body. RO7673396 is an experimental medicine. This means that health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved RO7673396 alone or in combination with other cancer medicines for the treatment of solid tumors.

This study aims to test how safe and effective RO7673396 is (at different doses) when given alone and in combination with Tam-Peli and to understand how the body processes the medicine.

2. Who can take part in the study?

People of at least 18 years of age can take part in the study if they have solid tumors with a confirmed change in the RAS gene or a very high chance to have this change. People must be able to provide fresh tumor tissue or previously collected and stored (archived) tissue samples.

People may not be able to take part in this study if they have any other significant health conditions or have a history of another type of cancer within the last 3 years. Women who are pregnant, intend to become pregnant, or currently breastfeeding cannot participate 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 for about 28 days before the start of the study treatment.

Everyone who joins this study will receive either RO7673396, Tam-Peli or a combination of both. RO7673396 will be given as a tablet to be taken by mouth at home, while Tam-Peli will be given as a drip into a vein every 3 weeks at the study hospital.

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 day for the first few days of study treatment and then once or twice a week thereafter. This is to see how well the study treatment is working and any unwanted effects participants may have. Participants will have a follow-up visit after completing the study treatment during which the study doctor will check on the participant’s well-being. Some participants will have further follow-up visits every 6 to 9 weeks to check whether the cancer has grown back. The total time of participation in the study may be more than 24 months. 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 results measured in the study to assess if the medicine has worked are the number of participants with unwanted effects and the number of participants who are cancer-free or have a reduction of their cancer. Other key results measured in the study include:

• How well the body processes RO7673396 when given alone or in combination with other cancer medicines.
• How much time there is between the person’s cancer first responding to the study treatment and the cancer getting worse.
• The time from the start of study treatment until the first sign of cancer worsening or participants passing away due to any cause.

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. 

The study involves some risks from the study treatment and procedures to the participants. It may not be fully known at the time of the study how safe and how well the study treatment works. 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 positive and negative 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 have regular check-ups to see if there are any unwanted effects. 

RO7673396
RO7673396 has had limited testing in humans. Participants will be told about the known unwanted effects of this drug as well as the possible unwanted effects, based on the results of the testing in humans so far, laboratory studies or knowledge of similar medicines. Possible unwanted effects include vomiting, feeling sick (nausea), diarrhea, increase in liver enzymes and liver damage, low levels of red blood cells (anemia, which may cause difficulty breathing and/or fatigue), low levels of platelet count (which may cause bleeding), low levels of white blood cell count and increased risk of infection, formation of blood clots (which may cause shortness of breath, heart attack and stroke), high levels of phosphate and buildup of minerals in different tissues in your body, decreased testes function and inability to father a child, and skin, lungs, heart and eye problems. 

As RO7673396 will be given as an oral tablet (given by mouth), additional possible unwanted effects include mouth sores, inflammation of mucous membrane throughout the digestive tract and holes in the wall of the digestive tract. 

Tambotatug Pelitecan (Tam-Peli)
Tam-Peli has had limited testing in humans. Participants will be told about the known unwanted effects of this drug as well as the possible unwanted effects, based on the results of the testing in humans so far, laboratory studies or knowledge of similar medicines. Important known unwanted effects include presence of bacteria in the blood (bacteremia), constipation, cough, decreased appetite, diarrhea, nausea, vomiting, decreased level of potassium in the blood (hypokalemia), decreased level of sodium in the blood (hyponatremia), decreased red blood cells or hemoglobin, a protein that carries oxygen in your blood (anemia), decreased lymphocytes, a type of white blood cell (lymphopenia), decreased neutrophil, a type of white blood cell (neutropenia), decreased white blood cell count (leukopenia) which may weaken immune system, decreased level of calcium in the blood (hypocalcemia), decreased albumin in the blood (hypoalbuminemia), excess amount of protein in the urine (proteinuria), excess uric acid levels in the blood (hyperuricemia), fatigue, hair loss (alopecia), high blood sugar (hyperglycemia), increased level of alkaline phosphatase in the blood, increased triglyceride in blood (hypertriglyceridemia), increased level of cholesterol in the blood (hypercholesterolemia), increased levels of liver enzymes (alanine aminotransferase increased, aspartate aminotransferase increased, and gammaglutamyl transferase increased), low platelets in the blood, which may make you more likely to bruise or bleed (thrombocytopenia), lung infection (pneumonia), painful inflammation or sore in the mouth or lips (stomatitis), sepsis, weight decreased and decreased neutrophil, a type of white blood cell, with fever (febrile neutropenia). 

Tam-Peli will be given as a drip into the vein (infusion). Known unwanted effects of an infusion include fever, chills, rash, and difficulty breathing. 

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.