AuthorisedTherapeutic confirmatory (Phase III)Interventional

J6M-MC-JSGD: A Phase 2, Randomized, Open-Label Dose Optimization and Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Tersolisib (LY4064809) Combined with a CDK4/6 Inhibitor and Endocrine Therapy in Adults with HR+, HER2- Advanced Breast Cancer with a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)

This study, called PIKALO-2, is looking for adults with advanced breast cancer that tests positive for hormone receptors (HR+), negative for HER2, and has a specific gene change called a PIK3CA mutation. Participants must not have received any prior treatment for their advanced breast cancer. The trial aims to find out if adding a new drug, tersolisib, to existing hormone treatments and CDK4/6 inhibitors (like palbociclib, ribociclib, or abemaciclib) can more effectively shrink tumours or slow down cancer growth. One part of the study will help doctors find the best dose of tersolisib, and another part will compare tersolisib with a dummy drug (placebo) to see how well it works. The main goals are to see how many people's tumours shrink and how long people live without their cancer getting worse.

At a glance

Status

Authorised

Phase

Therapeutic confirmatory (Phase III)

Sponsor

Eli Lilly & Co.

Enrolment target

274

Start

24 Mar 2026

Neoplasm Metastasis, Breast Neoplasms

What is this study about?

This clinical trial is for people with a specific type of advanced breast cancer. We call it 'advanced' because it has spread from where it started, or it just can't be removed with surgery. The type of breast cancer we're looking at is important: it must be positive for hormone receptors (HR+) and negative for HER2. This means its growth is often linked to hormones, and it doesn't have too much of a protein called HER2. Crucially, your cancer also needs to have a particular change in a gene called PIK3CA.

In this study, researchers are testing a new medicine called tersolisib. It's designed to work alongside treatments you might already know about, like hormone therapy (such as anastrozole, exemestane, fulvestrant, or letrozole) and another type of drug called a CDK4/6 inhibitor (like palbociclib, ribociclib, or abemaciclib). The idea is that combining tersolisib with these existing treatments might be more effective at shrinking tumours or stopping the cancer from growing.

The study has two main parts. The first part is about finding the best dose of tersolisib to use. The second, larger part, will compare the new treatment combination with tersolisib against standard treatment combined with a placebo (a dummy drug). This helps researchers understand if tersolisib truly makes a difference. They'll be watching closely to see how many people's tumours shrink or disappear, and how long people stay well without their cancer getting worse.

The goal of this research is to find better treatment options for people with advanced HR+, HER2- breast cancer with a PIK3CA mutation, potentially offering more effective ways to manage the disease and improve quality of life.

Key takeaways

This study is for adults with advanced HR+, HER2- breast cancer with a PIK3CA gene mutation.
You must not have had any previous treatment for your advanced breast cancer.
It tests a new drug, tersolisib, with standard hormone therapy and CDK4/6 inhibitors.
The study aims to see if this new combination can lead to better tumour shrinkage and slower cancer growth.
Participants will be closely monitored with regular tests for up to 5 years.

Who may be eligible?

To join this study, you need to be an adult, 18 years old or older. This study is open to both men and women.

Your breast cancer must be considered 'advanced,' meaning it has spread or is unable to be removed by surgery. It also needs to have specific characteristics: it must be hormone receptor positive (HR+) and HER2 negative. On top of that, your cancer must have a specific change in its genes called a "PIK3CA mutation."

Crucially, you must not have received any previous treatment specifically for your advanced breast cancer. This means if your cancer has spread, this would be your first treatment directed at the advanced disease.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 18 years old or older?
Has your breast cancer spread or is it not removable by surgery (advanced)?
Has your breast cancer been tested and confirmed to be HR+ and HER2-?
Has your breast cancer also been tested and found to have a PIK3CA gene mutation?
Have you NOT received any prior treatment specifically for your advanced breast cancer?

Answer every question to see your result.

What does participation involve?

If you decide to take part in this study, you will be given one of the study drugs, either tersolisib or a matching placebo (a dummy drug), along with a standard hormone therapy (like anastrozole, exemestane, fulvestrant, or letrozole) and a CDK4/6 inhibitor (like palbociclib, ribociclib, or abemaciclib). The study is planned to last for up to 5 years, or until your cancer gets worse or you decide to stop participating.

You will have regular appointments at the hospital or clinic. These visits will involve blood tests, physical examinations, and scans (like CT or MRI scans) to check how the treatment is working and monitor your health. You may also be asked to provide tissue samples or undergo other tests. The frequency of these visits might change over time, being more frequent at the beginning of the study and less so later on, but you will always be kept informed about your schedule.

The medical team will explain all the procedures in detail and ensure you understand what's involved before you commit to the study. It's important to know that you'll be closely monitored throughout your participation.

Potential risks and benefits

Taking part in a clinical trial might offer potential benefits, such as receiving a new investigational treatment like tersolisib that might be more effective than current options, and you'll receive very close medical monitoring. However, there are also potential risks; tersolisib is an experimental drug, meaning its full side effects and how it interacts with other medicines aren't completely known, and it might not work for everyone. You may experience side effects, some of which could be serious. You have the right to withdraw from the study at any time, for any reason, without it affecting your future medical care.

Locations (6)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

—
Unverified
Germany
—
Unverified
Greece
—
Unverified
France
—
Unverified
Spain
—
Unverified
Belgium
—
Unverified
Italy

Common questions

What is PIK3CA mutation?

It's a specific change in a gene within the cancer cells that can sometimes make breast cancer grow. This study is particularly looking for people with this gene change.

What is an HR+ HER2- breast cancer?

HR+ means the cancer cells have receptors for hormones, making their growth sensitive to them. HER2- means the cancer doesn't have high levels of the HER2 protein, so it won't be treated with HER2-targeted drugs.

What is a 'CDK4/6 inhibitor'?

These are drugs that block certain proteins involved in cell growth, which helps to slow down or stop cancer cells from dividing. Examples include palbociclib, ribociclib, and abemaciclib, which are often used for HR+ breast cancer.

What is a placebo?

A placebo is a 'dummy' drug that looks exactly like the actual medicine but contains no active ingredients. It's used in some parts of the study to help see if the new medicine is truly effective.

How long will the study last for me?

The study could last up to 5 years, or until your cancer gets worse, or you decide to stop participating. You will be closely monitored throughout this time.