Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer

(INAVO121 Trial)

Not currently recruiting at 326 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial explores the effectiveness and safety of two drug combinations for a specific type of breast cancer. It compares inavolisib (an experimental treatment) plus fulvestrant with alpelisib plus fulvestrant for patients with hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer that is advanced or has spread. The trial seeks participants whose cancer has worsened despite treatments like CDK4/6 inhibitors and hormonal therapy. Those experiencing progression with this type of breast cancer may qualify for the study. As a Phase 3 trial, it represents the final step before FDA approval, offering access to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the combination of inavolisib and fulvestrant is safe over the long term. Patients generally tolerate it well, and any side effects can be managed.

Research confirms that the combination of alpelisib and fulvestrant is effective and safe in real-world use. The FDA has already approved alpelisib for treating a similar type of breast cancer, so doctors are familiar with its safety.

Both treatments have been studied enough to provide confidence in their safety for those considering joining the trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Inavolisib and Alpelisib both target the same pathway but in slightly different ways to tackle breast cancer. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, these drugs target a specific part of cancer cell growth, the PI3K pathway, which is often altered in breast cancer. Inavolisib is a new PI3K inhibitor that might offer a more targeted approach than existing options, potentially leading to fewer side effects and improved effectiveness. Alpelisib, already in use for certain breast cancers, serves as a benchmark, but the hope is that Inavolisib will bring even better outcomes by being more selective in its action.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare the effectiveness of two treatment combinations for breast cancer with PIK3CA mutations: Inavolisib + Fulvestrant and Alpelisib + Fulvestrant. Research has shown that combining Inavolisib and Fulvestrant holds promise for treating breast cancer with PIK3CA mutations. In earlier studies, this combination, along with palbociclib, significantly improved patient survival and delayed cancer progression compared to a placebo. Patients experienced more than twice the time without their cancer worsening.

For the combination of Alpelisib and Fulvestrant, studies have shown it nearly doubled the time patients went without cancer progression in those with PIK3CA mutations. It has also proven effective in real-world settings, with many patients responding well to the treatment. Both treatment options in this trial show strong potential for managing this type of breast cancer. ^{1 2 3 4 6}

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: Sub-study: Inavolisib + Fulvestrant + CYP substrates Experimental Treatment 5 Interventions

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

Group II: Inavolisib + Fulvestrant Experimental Treatment 2 Interventions

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

Group III: 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 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]

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, 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]

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 (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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9631302/

Real world outcomes with alpelisib in metastatic hormone ...

The median duration of response was 5.77 months (range: 5.54, 8.98). At the time of this report, 8/27 (29.6%) patients had died, and all deaths were attributed ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13058

metastatic breast cancer in real-world clinical practice.

The results of using alpelisib with fulvestrant confirm its effectiveness in real-world clinical practice in patients with pre-treated HR+HER2- negative ...

3.

piqray-hcp.com

piqray-hcp.com/metastatic-breast-cancer/efficacy/efficacy-results

Efficacy Results | PIQRAY® (alpelisib) tablets

PIQRAY + fulvestrant nearly doubled mPFS in patients with a PIK3CA driver mutation. At the prespecified final OS analysis, there was no significant difference ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33246021/

final overall survival results from SOLAR-1

The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1813904

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive ...

In a phase 1b trial, alpelisib plus fulvestrant led to a complete or partial response in 29% of patients with heavily pretreated PIK3CA-altered ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02437318

NCT02437318 | Study Assessing the Efficacy and Safety of ...

This was a randomized, double-blind, placebo-controlled, international multicenter Phase III study that evaluated the efficacy and safety of treatment with ...