A study to assess the safety, tolerability, metabolism in the body, and efficacy of RO7276389 alone or in combination with Cobimetinib for the treatment of BRAF-mutated solid tumors or melanomas

Summary description of the study

With this study, we aim to find out: 1. what maximum dose participants can tolerate or what the recommended dose of RO7276389 alone or in combination with Cobimetinib should be 2. how safe RO7276389 alone or in combination with Cobimetinib is at different doses and what side effects this treatment may have 3. whether RO7276389 alone or in combination with Cobimetinib is effective against BRAF-mutated solid tumors or melanomas (a form of skin cancer) 4. how RO7276389 alone or in combination with Cobimetinib is distributed in the body and eliminated from the body 5. what effect food has on the distribution of RO7276389 alone or in combination with Cobimetinib in the body and on its elimination from the body Who can participate? Individuals over 18 years old with a BRAF-mutated solid tumor. The study will be conducted in two phases: Dose escalation: Here, patients receive the study treatment at a certain dose. If this dose is deemed tolerable, the next participant group receives a higher dose. The dose a participant receives is increased if the doctors assess the treatment as effective; it is reduced if side effects occur. The effect of food on the distribution and elimination of the study treatment is also investigated. Dose expansion: Here, a larger participant group is included. All participants receive the same dose of the study treatment. The dose in phase 2 is based on the results from phase 1.

(BASEC)

Intervention under investigation

Patients may be asked to participate in the study for up to 24 months.

It includes:

- A pre-screening phase of up to 28 days before the start of the study, during which examinations will determine if patients are eligible for study participation.

- A treatment phase, during which participants receive RO7276389 alone or in combination with Cotellic® (Cobimetinib) in treatment cycles of 4 weeks. Participants receive the study treatment both in the hospital under the supervision of a doctor and at a location specified by the participant.

- A follow-up phase, in which an examination of participants is scheduled 28 days after the last administration of RO7276389 and Cotellic® (Cobimetinib).

Participants will be assigned to one of the following treatment groups.

RO7276389 group: Up to three of the first participants enrolled in the study will receive a single dose of RO7276389 to examine how the drug is distributed and eliminated from the body. After three days, participants will receive the investigational drug every morning as a tablet with a full glass of water. The dose for newly enrolled patients will be adjusted based on the test results of previous participants. Participants who are enrolled in the study at a later time will receive higher doses of the investigational drug.

RO7276389 and Cobimetinib group: Participants will receive RO7276389 in the form of tablets, to be taken once daily for 28 consecutive days (= 1 cycle) along with Cobimetinib tablets; the latter will be taken for 21 consecutive days. Cobimetinib will not be administered from day 21 to day 28 of the treatment cycle.

Participants continue the regular intake of RO7276389 alone or in combination with Cobimetinib as long as the cancer does not worsen, no serious side effects occur, or they do not decide to withdraw from the study. Treatment may also be stopped earlier if the investigator believes that a participant is not benefiting from this treatment. After the last administration of the study treatment, the investigator will ask participants to undergo a follow-up examination every 3 months as long as they agree.

(BASEC)

Disease under investigation

The purpose of this study is to evaluate an unapproved drug (investigational product) called RO7276389, administered to study participants with solid tumors either alone or in combination with the drug Cobimetinib. Some solid tumors have a genetic alteration that leads to an abnormal change (mutation) in a body protein known as the BRAF protein. This altered BRAF protein changes the exchange of information within cells and can therefore cause cancer. Currently available cancer drugs that block the altered BRAF protein are less effective for cancer forms that spread to the brain. RO7276389 is an investigational product that has been approved by health authorities for the treatment of participants in a clinical trial who have advanced cancer with BRAF mutation, either alone or in combination with Cobimetinib. Cobimetinib is a cancer drug that blocks the MEK protein, which promotes the growth of cancer cells.

(BASEC)

Sponsor

Roche Pharma (Schweiz) AG

(BASEC)