Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer

(INAVO121 Trial)

Recruiting at 276 trial locations

Overseen By Reference Study ID Number: WO43919 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: LHRH agonists

Must not be taking: PI3K inhibitors, AKT inhibitors

Disqualifiers: Diabetes, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing two drug combinations to find out which one is better for treating a specific type of advanced breast cancer that hasn't responded to previous treatments. The drugs work by stopping cancer cells from growing and spreading.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on Type 2 diabetes medication, you cannot participate. Also, you cannot be on chronic therapy of 10 mg or more of prednisone per day or an equivalent dose of other corticosteroids or immunosuppressants.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on a PI3K, AKT, or mTOR inhibitor, or have Type 2 diabetes requiring treatment, you may not be eligible to participate.

What safety data is available for the treatment of Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for breast cancer?

The safety data for Alpelisib (Piqray) combined with Fulvestrant (Faslodex) in treating PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer includes findings from several studies. The SOLAR-1 trial showed that common adverse reactions were increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine aminotransferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time, and alopecia. In the French early access program, 39.1% of patients discontinued Alpelisib due to adverse events. The safety profile of Alpelisib requires careful patient selection and monitoring, especially regarding baseline glycemic status, due to the risk of hyperglycemia. No specific safety data for Inavolisib combined with Fulvestrant was provided in the research. ^{1 2 3 4 5}

Is the combination of Inavolisib + Fulvestrant or Alpelisib + Fulvestrant safe for treating breast cancer?

The combination of Alpelisib (also known as Piqray) and Fulvestrant (also known as Faslodex) has been studied for safety in breast cancer treatment. Common side effects include high blood sugar, diarrhea, rash, and nausea. It's important for patients to be monitored closely, especially for blood sugar levels, as some patients discontinued treatment due to adverse effects. ^{1 2 3 4 5}

Is the drug Alpelisib, Fulvestrant, Inavolisib a promising treatment for breast cancer?

Yes, the drug combination of Alpelisib and Fulvestrant is promising for treating a specific type of breast cancer. It has been shown to help patients with hormone receptor-positive, HER2-negative breast cancer that has a PIK3CA mutation. Studies have shown that it can extend the time patients live without the cancer getting worse. ^{1 3 4 5 6}

What makes the drug combination of Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant unique for breast cancer?

The combination of Alpelisib and Fulvestrant is unique because it targets breast cancer with a specific PIK3CA mutation, using Alpelisib, a PI3K inhibitor, to improve progression-free survival in hormone receptor-positive, HER2-negative breast cancer. This approach is particularly beneficial for patients who have already undergone multiple treatments, although it may cause side effects like high blood sugar, rash, and diarrhea. ^{1 3 4 5 6}

What data supports the idea that Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer is an effective drug?

The available research shows that Alpelisib combined with Fulvestrant is effective for treating a specific type of breast cancer. In studies, patients with a certain genetic mutation (PIK3CA) who took Alpelisib and Fulvestrant had a longer time before their cancer got worse compared to those who did not take Alpelisib. For example, in one study, the time before the cancer progressed was about 11 months for those on Alpelisib and Fulvestrant, compared to about 5.7 months for those who did not take Alpelisib. However, there is no specific data provided on Inavolisib combined with Fulvestrant, so we cannot compare its effectiveness directly to Alpelisib combined with Fulvestrant based on the information available. ^{1 3 4 5 7}

What data supports the effectiveness of the drug combination of Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for breast cancer?

The combination of alpelisib and fulvestrant has been shown to improve progression-free survival in patients with hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutations, as demonstrated in the SOLAR-1 trial. This combination was approved by the FDA based on its ability to extend the time patients lived without their cancer worsening compared to fulvestrant alone. ^{1 3 4 5 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with HR-positive, HER2-negative, PIK3CA mutated advanced or metastatic breast cancer who've progressed after CDK4/6i and endocrine therapy. They should have a life expectancy over 6 months, an ECOG status of 0-2, and no more than two prior systemic therapies in the metastatic setting (one chemo allowed). Pre/perimenopausal women must be on LHRH agonist therapy.

Inclusion Criteria

You are expected to live for more than 6 months.

My blood and organs are functioning well enough to start treatment.

My breast cancer progressed after treatment with CDK4/6 inhibitors and hormone therapy, with no more than 2 treatments in the metastatic setting.

Exclusion Criteria

I have had leptomeningeal disease or carcinomatous meningitis.

I have Type 2 diabetes and am on treatment, or I have a history of Type 1 diabetes.

My cancer returned more than a year after completing CDK4/6 inhibitor therapy, with no treatment for its spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either inavolisib plus fulvestrant or alpelisib plus fulvestrant

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Fulvestrant
• Inavolisib

Trial Overview The study compares the effectiveness and safety of Inavolisib plus Fulvestrant versus Alpelisib plus Fulvestrant in patients whose breast cancer has worsened despite previous treatments. It's a Phase III trial where participants are randomly assigned to one of these treatment combinations.

How Is the Trial Designed?

Group I: Inavolisib + Fulvestrant Experimental Treatment 2 Interventions

Participants will be administered the treatments as outlined in the interventions section.

Group II: Alpelisib + Fulvestrant Active Control 2 Interventions

Participants will be administered the treatments as outlined in the interventions section.

Alpelisib is already approved in United States, European Union for the following indications:

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

In a study of 247 patients with metastatic hormone receptor-positive, PIK3CA-mutant breast cancer, 61.5% developed any-grade hyperglycemia after treatment with alpelisib, with a median onset time of just 16 days.

Patients receiving alpelisib as standard care experienced significantly higher rates of hyperglycemia compared to those in clinical trials, highlighting the importance of monitoring and optimizing glycemic status before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Shen, S., Chen, Y., Carpio, A., et al.[2023]

In a real-life study of 233 patients with advanced breast cancer who had PIK3CA mutations, treatment with alpelisib and fulvestrant resulted in a median progression-free survival (PFS) of 5.3 months, indicating its efficacy even after multiple prior treatments.

However, 39.1% of patients discontinued alpelisib due to adverse events, highlighting the importance of monitoring for side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. Bello Roufai, D., Gonçalves, A., De La Motte Rouge, T., et al.[2023]

Alpelisib (Piqray™) is an oral PI3K inhibitor specifically targeting PI3Kα, showing efficacy in treating hormone receptor-positive, HER2-negative breast cancer in patients with a PIK3CA mutation.

The drug has been approved in the USA for use in combination with fulvestrant, marking a significant milestone in its development for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. Markham, A.[2020]

Alpelisib (PIQRAY®) is the first PI3K inhibitor approved for treating hormone receptor-positive metastatic breast cancer with PIK3CA mutations, showing promising clinical results that support its use in overcoming endocrine resistance.

The review highlights the pharmacodynamic and pharmacokinetic properties of alpelisib, along with safety and efficacy data from the Phase III SOLAR-1 trial, which led to its FDA approval, indicating its potential as a tailored treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. Mavratzas, A., Marmé, F.[2021]

Alpelisib, when combined with fulvestrant, significantly improves progression-free survival (PFS) in postmenopausal women and men with hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer, showing a median PFS of 11 months compared to 5.7 months with placebo.

The treatment is specifically effective for patients with PIK3CA mutations, as no PFS benefit was observed in those without these mutations, highlighting the importance of genetic testing in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer. Narayan, P., Prowell, TM., Gao, JJ., et al.[2022]

Alpelisib, a PI3K-alpha inhibitor, has been approved for use with fulvestrant in patients with HR+/HER2- breast cancer that have PIK3CA mutations, showing improved progression-free survival compared to fulvestrant alone in a phase III trial.

While alpelisib offers a significant benefit in delaying disease progression, its safety profile necessitates careful patient selection and monitoring, particularly regarding glycemic levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. Leenhardt, F., Alexandre, M., Jacot, W.[2021]

In a retrospective analysis of 33 patients with HR+, HER2- metastatic breast cancer, the combination of alpelisib and fulvestrant showed worse outcomes in heavily pretreated patients compared to those receiving it as a first-line treatment, with significant rates of disease progression and treatment discontinuation.

Adverse effects were common, with hyperglycemia (66.7%), rash (45.5%), and diarrhea (72.7%) leading to hospitalizations and pharmacological treatment, raising concerns about the tolerability of this regimen in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alpelisib in breast cancer: A real-world analysis. Miller, J., Armgardt, E., Svoboda, A.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alpelisib in breast cancer: A real-world analysis. [2023]