Inavolisib + CDK4/6 Inhibitor + Letrozole for Breast Cancer

(INAVO123 Trial)

Recruiting at 221 trial locations

Overseen By Reference Study ID Number: WO45654 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: CDK4/6 inhibitors, Letrozole

Must not be taking: Strong CYP3A4 inhibitors, inducers

Disqualifiers: Type 1 diabetes, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced breast cancer that is hormone-sensitive, HER2-negative, and has a specific gene mutation. Researchers aim to determine if adding inavolisib, a potential new drug, to standard treatment with letrozole and a CDK4/6 inhibitor is more effective than using a placebo with the standard treatment. The trial includes individuals whose cancer hasn't spread during previous hormone treatments and who have a specific type of breast cancer. If this matches your situation, you might be a suitable candidate for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong CYP3A4 inhibitors or inducers at least 4 weeks before starting the study treatment. If you're on these medications, you may need to discuss alternatives with your doctor.

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

Research shows that combining inavolisib with letrozole and a CDK4/6 inhibitor is generally well-tolerated by patients. Studies have found that this treatment has a manageable safety profile, with serious side effects being rare. Most patients can continue the treatment without interruption due to side effects. Specifically, few patients have discontinued treatment due to adverse effects, indicating that the treatment is relatively safe for most individuals. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Researchers are excited about inavolisib combined with letrozole and a CDK4/6 inhibitor because it introduces a new approach to treating breast cancer. Unlike the standard treatments that primarily focus on hormone receptor pathways, inavolisib targets the PI3K pathway, which is often involved in cancer cell growth. This novel mechanism could potentially enhance the effectiveness of existing therapies by addressing multiple pathways that contribute to tumor development. The combination of these treatments could lead to improved outcomes for patients by offering a more comprehensive attack on cancer cells.

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

Research has shown that combining inavolisib, letrozole, and a CDK4/6 inhibitor may effectively treat certain advanced breast cancers. In this trial, participants will receive either inavolisib, letrozole, and a CDK4/6 inhibitor or a placebo with letrozole and a CDK4/6 inhibitor. Past studies demonstrated that the combination including inavolisib slowed disease progression and extended survival, particularly for patients with a specific gene mutation called PIK3CA, who have hormone receptor-positive and HER2-negative breast cancer. Specifically, patients who had already used a CDK4/6 inhibitor experienced a clinical benefit rate of up to 48.3% when inavolisib and letrozole were added to their treatment. This suggests that including inavolisib could significantly aid in managing this type of breast cancer. ^{1 2 4 5 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 men and women with advanced breast cancer that's hormone receptor-positive, HER2-negative, and has a specific mutation (PIK3CA). They should have measurable disease, be in good physical condition (ECOG 0 or 1), and either be newly diagnosed or relapsed after at least two years of standard treatment without progression.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer has the specific biomarker needed for this trial.

My cancer can be measured using specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inavolisib plus a CDK4/6 inhibitor and letrozole or placebo plus a CDK4/6 inhibitor and letrozole

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CDK4/6i
• Inavolisib

Trial Overview The study tests the effectiveness of Inavolisib combined with a CDK4/6 inhibitor and Letrozole against a placebo plus the same CDK4/6 inhibitor and Letrozole. It aims to see if adding Inavolisib improves outcomes for patients with certain genetic features in their tumors.

How Is the Trial Designed?

Group I: Inavolisib + Letrozole + CDK4/6i Experimental Treatment 3 Interventions

Participants will receive inavolisib, letrozole and CDK4/6i.

Group II: Placebo + Letrozole + CDK4/6i Placebo Group 3 Interventions

Participants will receive placebo, letrozole and CDK4/6i.

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

Citations

1. roche.com roche.com/media/releases/med-cor-2025-01-28

Roche's Itovebi demonstrated statistically significant and ... "The INAVO120 overall survival results show that the Itovebi-based regimen not only delayed disease progression, but also helped people with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06790693

NCT06790693 | A Study Evaluating the Efficacy and Safety ... This study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925001789

Inavolisib plus letrozole or fulvestrant in PIK3CA-mutated, ... In all patients who had previously received a CDK4/6 inhibitor, the clinical benefit rate was 31·0 % in the inavolisib plus letrozole arm and 48·3 % in the ...

4. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473372

After a CDK4/6 Inhibitor: State of the Art in Hormone ... Preclinical data have shown that BTX-9341 achieves deeper, more durable CDK4/6 suppression than traditional dual inhibitors, maintains potency in palbociclib- ...

5. onclive.com onclive.com/view/inavolisib-plus-palbociclib-fulvestrant-shows-os-benefit-in-endocrine-resistant-pik3ca-mutated-hr-her2-breast-cancer

Inavolisib Plus Palbociclib/Fulvestrant Shows OS Benefit ... Inavolisib with palbociclib and fulvestrant improved overall survival in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer. The ...

6. esmoopen.com esmoopen.com/article/S2059-7029(25)01172-X/fulltext

Safety overview and management of inavolisib alone ... Here, we describe in detail the safety and tolerability of inavolisib alone and in combination with endocrine therapy (letrozole or fulvestrant ...