A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of RO7616789 in Advanced Small Cell Lung Cancer and Other Neuroendocrine Carcinomas

1. Why is the TRIDENIS clinical trial needed?

The neuroendocrine system is made up of nerves and gland cells that produce hormones. Small cell lung cancer (SCLC) is a type of neuroendocrine cancer (known as ‘neuroendocrine carcinoma’, or NEC). Standard first treatment of SCLC and other NECs includes chemotherapy and/or medicines that encourage the body’s immune system to attack tumours (known as ‘immunotherapy’). However, new treatments are needed that improve health outcomes for people living with SCLCs that have grown or spread to other parts of the body (also called ‘advanced SCLC’) or with other fast-growing (also known as ‘high-grade’) NECs.

More than 2 in 3 people with NEC have cancer cells that contain a protein called DLL3, which helps cancer cells to grow. RO7616789 is a new type of immunotherapy drug that attaches to DLL3 on cancer cells and, at the same time, attaches to immune cells, which brings them closer to cancer cells and activates the immune cells to fight cancer cells. In this clinical trial, RO7616789 will be given to people for the first time to look at how safe and effective different doses are against SCLC and other NECs.  

2. How does the TRIDENIS clinical trial work?

This clinical trial is recruiting people who have a medical condition called SCLC or another type of NEC. People can take part if they have advanced SCLC or high-grade NEC that has stopped responding to standard treatment (also called ‘relapsed’). 

The purpose of this clinical trial is to find out whether RO7616789 at different doses has any effects (good or bad), what happens to RO7616789 once it is in the body, and what RO7616789 does to the body.

The trial is split into three parts; each participant will be placed in one of three parts:

●      Part 1 will assess how safe and how well different doses of RO7616789 work when given once a week

●      Part 2 will assess how safe and how well different doses of RO7616789 work when given once every 3 weeks

In Parts 1 and 2, the dose of RO7616789 given may be the same every time, or lower doses may be given for the first few times (called ‘step-up’ dosing) followed by the intended higher dose every time after that. 

In Part 2, the first two doses of RO7616789 may be given as follows (instead of every three weeks):

●        One week apart and the third dose two weeks later, then every 3 weeks from then on, or

●        One week apart and the third dose one week later, then every 3 weeks from then on

The results of Parts 1 and 2 will help researchers decide the safest and most effective doses of RO7616789 and how often they should be given for Part 3. 

●      Part 3 will have more participants than Parts 1 and 2, and RO7616789 will be given depending on the safest and most effective dose results of Parts 1 and 2

Participants will be given the clinical trial treatment RO7616789 for up to 2 years, or until their cancer gets worse, they have unacceptable side effects, or they choose to leave the trial. Participants will be required to stay in hospital to be monitored for at least 3 days after being given RO7616789 for the first time, and may need to stay in hospital after being given each ’step-up’ dose and the intended highest dose of RO7616789 for the first time.

Participants will be seen by the clinical trial doctor regularly and at least once a week for the first 2 months. These hospital visits will include checks such as scans and heart monitoring to see how the participant is responding to the treatment and any side effects they may be having. Participants’ total time in the clinical trial will depend on how their cancer responds to the clinical trial treatment. This could range from 1 day to more than 2 years. After being given the final dose of clinical trial treatment, the trial doctor will follow up with participants every 3 months for as long as they agree to it. Participants are free to stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the TRIDENIS clinical trial?

The main clinical trial endpoints (the main results that are measured in the trial to see if the medicine has worked) are:

●      The number and seriousness of side effects

●      What happens to RO7616789 at different doses once it is in the body, and the maximum dose of RO7616789 that can be given before unacceptable side effects occur

●      How many participants have a positive response to treatment (objective response rate)

●      How much time passes between participants’ first responding to treatment and cancer getting worse (known as ‘duration of response’)

●      How long participants live (overall survival)

The other clinical trial endpoints include:

●      How RO7616789 moves around the body

●      How the body’s immune system interacts with RO7616789 

4. Who can take part in this clinical trial?

People can take part in this trial if they are at least 18 years of age and have been diagnosed with advanced SCLC or another NEC that has relapsed after at least one previous treatment. Participants in Part 3 must allow for a sample of their cancer to be examined to find out how much DLL3 is on the surface of their cancer cells - the sample may have been already taken as part of the participants’ usual medical care or can be taken as part of this trial.

People may not be able to take part in this trial if they have previously received certain anti-cancer medicines, including immunotherapies, within a certain time before starting the trial or if they have had a serious reaction to previous anti-cancer therapies. People may also not be able to take part in this trial if:

●      They have received certain other treatments

●      Their cancer has spread to the brain or spinal cord, causes symptoms, and is untreated or is currently being treated with certain medicines

●      They have certain other medical conditions such as other cancers, heart disease, uncontrolled type 2 diabetes, or have had a recent epileptic seizure or stroke

●      They are pregnant or breastfeeding or are planning to become pregnant during or soon after the trial 

The clinical trial doctor will decide who can take part in the trial. 

5. What treatment will participants be given in this clinical trial?

Everyone who joins this clinical trial will be given:

●      RO7616789, given regularly (weekly or every three weeks) as an infusion (into the vein) for up to 2 years, unless cancer gets worse, there are unacceptable side effects, or if participants choose to leave the trial

If a participant experiences a potential side effect called ‘cytokine release syndrome’ (CRS), they may receive another drug called tocilizumab.

This is an open-label trial, which means everyone involved, including the participants and the doctors, know which clinical trial drugs and which doses are being used.

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant, although it may not be greater than the risks related to routine medical care or the natural progression of the health condition. Potential participants will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. These will all be described in an informed consent form (a document that provides people with the information they need to make a decision to volunteer for a clinical trial). A potential participant should also discuss these with members of the research team and with their usual healthcare provider. Anyone interested in taking part in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.

Risks associated with the clinical trial drugs

Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening and can vary from person to person.

RO7616789

RO7616789 has not yet been tested in humans. For this reason, the side effects of this drug are not known at this time. Potential participants will be told about the potential side effects, based on laboratory studies or knowledge of similar drugs.

Tocilizumab

Potential participants will be told about the known side effects of tocilizumab, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.

RO7616789 and tocilizumab will be given as an infusion (into the vein) of an arm. Participants will be told about any known side effects of infusions. 

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.

For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05619744