A clinical trial to compare inavolisib plus fulvestrant versus alpelisib plus fulvestrant in people with hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer that has spread during or after treatment with a CDK4/6 inhibitor plus hormone (endocrine) therapy

1. Why is the INAVO121 clinical trial needed?

The most common type of breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. HR-positive, HER2-negative breast cancer can spread to nearby cells (known as ‘locally advanced’ cancer) or to other parts of the body (known as ‘metastatic’ cancer).

Standard treatment options for patients with HR-positive, HER2-negative metastatic breast cancer includes endocrine therapy, endocrine therapy combined with a type of drug called a CDK4/6 inhibitor, or chemotherapy. However, in most people with this type of breast cancer, the cancer eventually comes back (known as ‘relapse') because the treatments have stopped working.

Sometimes, cancer cells can have a changed version (also known as a ‘mutation’) of a gene called PIK3CA. Breast cancers with this type of mutation can relapse more quickly after standard treatment has been given.

Drugs such as inavolisib or alpelisib block the activity of this mutated PIK3CA gene to slow the growth of cancer cells and may be effective treatments after standard treatment stops working. Alpelisib, used with the endocrine treatment fulvestrant, is an approved treatment in some countries for patients with HR-positive, HER2-negative breast cancer with a PIK3CA mutation that has spread after standard endocrine therapy. 

Inavolisib is an experimental treatment, which means health authorities have not approved it for the treatment of breast cancer or any other conditions. In this trial, researchers are looking at how well inavolisib works when given with fulvestrant compared with alpelisib plus fulvestrant, in people with HR-positive, HER2-negative breast cancer. 

2. How does the INAVO121 clinical trial work?

This clinical trial is recruiting people who have a health condition called HR-positive, HER2-negative breast cancer that has a mutation in a gene called PIK3CA. People can take part if their cancer is locally advanced or metastatic and has not responded to previous treatment with a CDK4/6 inhibitor plus endocrine therapy.

The purpose of this clinical trial is to compare the effects, good or bad, of inavolisib plus fulvestrant versus alpelisib plus fulvestrant in people with HR-positive, HER2-negative, PIK3CA-mutated breast cancer. People who take part in this clinical trial will receive either inavolisib plus fulvestrant or alpelisib plus fulvestrant.

Participants will be given the clinical trial treatment inavolisib plus fulvestrant OR alpelisib plus fulvestrant for as long as it can help them. Participants will be seen by the clinical trial doctor weekly during the first month of treatment and approximately once a month after that. These hospital visits will include checks to see how the participant is responding to the treatment and any side effects they may be having. After the final dose of the clinical trial treatment and the 30 days safety follow-up visit, the trial doctor will follow-up with participants by telephone or clinic visits approximately every 3 months for as long as they agree to it. Participants’ total time in the clinical trial will depend on how their breast cancer responds to the clinical trial treatment and future follow-up treatments. This could range from 1 day to more than 7 years (including time on clinical trial treatment and time in follow-up). Participants are free to stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the INAVO121 clinical trial?

The main clinical trial endpoint (the main result that is measured in the trial to see if the treatment has worked) is how long participants live without their cancer getting worse (known as ‘progression-free survival’).

The other clinical trial endpoints are:

●      How long participants live (known as ‘overall survival’)

●      How many participants have a change in their tumour size or how much their cancer has progressed (known as ‘overall response rate’)

●      How much time passes between when participants’ cancer first responds to treatment and when their cancer appears to get worse (known as ‘duration of response’)

●      The number of participants who respond to treatment (known as ‘best overall response’)

●      The number of participants who respond to treatment or have tumours that stay the same size for at least approximately 6 months (known as ‘clinical benefit rate')

●      How much time passes from the start of the trial to when participants:

       o   feel less pain, or

       o   cancer appears to interfere less with their daily activities, or

       o   report an improved health-related quality of life

●      The number and seriousness of any side effects 

4. Who can take part in this clinical trial?

People can take part in this trial if they are over 18 years old and have HR-positive, HER2-negative, PIK3CA-mutated breast cancer that has spread during or after treatment with a combination of a CDK4/6 inhibitor plus endocrine therapy.

People may not be able to take part in this trial if their cancer has spread to the brain or spinal cord and is untreated or is currently being treated. Or if they have certain other medical conditions, such as diabetes or an eye condition, that will require treatment during the trial. People may also be unable to take part in this trial if they have previously received certain treatments, if they are pregnant or breastfeeding or are planning to become pregnant.

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

Everyone who joins this clinical trial will be split into two groups randomly (like flipping a coin) and given either:

●        Group 1: inavolisib given as a single tablet (to be swallowed) once every day, and fulvestrant given as an injection into a muscle (intramuscular) once every two weeks during the first month, then once a month

OR

●        Group 2: alpelisib given as two tablets (to be swallowed) once every day, and fulvestrant given as an injection into a muscle (intramuscular) once every two weeks during the first month, then once a month

Participants will have an equal chance of being placed in either group.

This is an open-label trial, which means everyone involved, including the participants and the doctors, will know which clinical trial drugs each participant has been given. 

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 document (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.

Inavolisib, alpelisib and fulvestrant

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

Inavolisib and alpelisib will be given as oral tablets to be swallowed. Participants will be told about any known side effects of taking oral tablets.

Fulvestrant will be given by intramuscular injection, which will involve inserting a needle into a muscle of the upper buttocks. Participants will be told about any known side effects of intramuscular injection.

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