Inavolisib Combination for Breast Cancer

(INAVO120 Trial)

Not currently recruiting at 339 trial locations

Overseen By Reference Study ID Number: WO41554 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Hoffmann-La Roche

Must be taking: LHRH agonists

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Diabetes, CNS metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 9

Duration: Up to 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with a specific type of breast cancer that has returned or spread despite earlier treatment. It evaluates the effectiveness of inavolisib (a potential new drug) combined with palbociclib and fulvestrant, compared to a placebo with the same drugs, in individuals with a PIK3CA mutation and HR-positive, HER2-negative breast cancer. This trial targets those whose cancer progressed during or shortly after hormone therapy. Ideal participants have not received other treatments for their metastatic cancer and possess the specific gene mutation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain diabetes medications, chronic corticosteroids, or have had recent anti-cancer therapy or investigational drugs.

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

Research has shown that the combination of inavolisib, palbociclib, and fulvestrant is generally safe. While some side effects might occur, they can usually be managed or treated. In earlier studies, patients experienced some side effects, but these were mostly manageable and did not require stopping the treatment.

When used together, inavolisib, palbociclib, and fulvestrant have shown promising results, reducing the risk of death by over 30% compared to other treatments. This suggests that the benefits of this treatment might outweigh the potential risks for many patients. However, since everyone reacts differently, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Inavolisib offers a new approach to tackling breast cancer. Unlike standard treatments, which primarily focus on blocking hormone receptors or inhibiting cell division, Inavolisib targets the PI3K pathway, a crucial signaling pathway involved in cancer cell growth and survival. By combining Inavolisib with Fulvestrant and Palbociclib, the treatment may provide a more comprehensive attack on cancer cells, potentially leading to improved outcomes for patients. This novel mechanism of action is what makes Inavolisib stand out and holds promise for advancing breast cancer treatment.

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

This trial will compare two treatment combinations for PIK3CA-mutated, hormone receptor-positive, HER2-negative breast cancer. Participants in one arm will receive inavolisib, palbociclib, and fulvestrant. Studies have shown that inavolisib, when combined with palbociclib and fulvestrant, significantly extends the time patients live without cancer progression. Specifically, patients taking inavolisib experienced an average of 15 months without cancer worsening, compared to 7.3 months for those on a placebo. This combination also reduces the risk of death by more than 30% for patients with this breast cancer type. These findings suggest a promising benefit for those considering joining the trial. ^{2 6 7 8 9}

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 a specific mutation in their breast cancer cells (PIK3CA), whose cancer has worsened during or after hormone therapy and haven't had treatment for advanced disease. They must have measurable disease, provide tissue samples, have good organ function, not be pregnant or breastfeeding, and can't have untreated brain metastases or prior treatments that are excluded.

Inclusion Criteria

My cancer has a specific genetic change in the PIK3CA gene.

You are expected to live for more than 6 months.

My cancer can be measured by scans and is not limited to only my bones.

Exclusion Criteria

I have not taken fulvestrant or similar drugs for more than 6 months, except as part of early treatment.

I do not have active eye infections or conditions needing surgery soon.

I have not had major surgery or a significant injury in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inavolisib, palbociclib, and fulvestrant or placebo, palbociclib, and fulvestrant

Up to 6 years

Day 1 of Cycles 1-3, then Day 1 of every other cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Every 8 weeks for 2 years, then every 12 weeks thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Inavolisib
• Palbociclib

Trial Overview The study tests the effectiveness of Inavolisib combined with Palbociclib and Fulvestrant versus a placebo plus Palbociclib and Fulvestrant in treating certain advanced breast cancers. It aims to see if adding Inavolisib helps patients better than the standard treatment alone.

How Is the Trial Designed?

Group I: Inavolisib + Palbociclib + Fulvestrant Experimental Treatment 3 Interventions

Participants will receive inavolisib, palbociclib, and fulvestrant.

Group II: Placebo + Palbociclib + Fulvestrant Placebo Group 3 Interventions

Participants will receive placebo, palbociclib, and fulvestrant. Participants randomized to the placebo arm who are still deriving benefit from the study treatment will be given an optional opportunity to crossover to the inavolisib arm.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

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 the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Palbociclib, in combination with letrozole, is FDA-approved for treating postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, showing its efficacy as an initial therapy.

The combination of palbociclib with fulvestrant has been found to provide better outcomes than fulvestrant alone for patients who have previously progressed on endocrine therapy, highlighting its potential in advanced treatment scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Lu, J.[2022]

The FDA approved palbociclib (IBRANCE) for use in men with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, expanding its indications beyond women, based on data from the PALOMA-2 and PALOMA-3 trials.

The approval was supported by safety data from phase I studies and real-world evidence, confirming that palbociclib is a viable treatment option for male patients with this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. Wedam, S., Fashoyin-Aje, L., Bloomquist, E., et al.[2021]

Fulvestrant 500 mg significantly improves the clinical benefit rate (CBR) in postmenopausal women with hormone receptor-positive advanced breast cancer compared to other endocrine therapies, based on a meta-analysis of six randomized controlled trials involving 1588 patients.

The analysis showed that fulvestrant 500 mg was particularly effective as a first-line treatment, with a notable odds ratio of 1.33 indicating a higher proportion of patients achieving a complete or partial response or stable disease for at least 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. Robertson, JFR., Jiang, Z., Di Leo, A., et al.[2020]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

The combination of everolimus, letrozole, and trastuzumab was found to be safe and showed promising anticancer activity in a study of 32 patients with treatment-refractory hormone receptor-positive, HER2-positive advanced cancers.

Partial responses were observed in five breast cancer patients, indicating potential effectiveness, while specific adverse events like hyperglycemia and mucositis were noted, helping to establish a recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Everolimus, Letrozole, and Trastuzumab in Patients with Hormone Receptor-positive Metastatic Breast Cancer or Other Solid Tumors. Ballhausen, A., Wheler, JJ., Karp, DD., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1052

Long-term safety of inavolisib (GDC-0077) in an ongoing ... Conclusions: These data indicate acceptable long-term tolerability. The safety profile of pts on study treatment with inavolisib alone or in ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT363596

Long-term safety of inavolisib (GDC-0077) in an ongoing ... Conclusions: These data indicate acceptable long-term tolerability. The safety profile of pts on study treatment with inavolisib alone or in combo with ...

3. roche.com roche.com/media/releases/med-cor-2025-05-31

New data show Roche's Itovebi significantly extended ... The ItovebiTM (inavolisib)-based regimen reduced the risk of death by more than 30% in people with PIK3CA-mutated HR-positive, HER2-negative ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40454641/

Overall Survival with Inavolisib in PIK3CA-Mutated ... Conclusions: Treatment with inavolisib plus palbociclib-fulvestrant led to a significant overall survival benefit, as compared with placebo plus ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2404625

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced ... The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1003

INAVO120: Phase III trial final overall survival (OS) analysis ... INAVO + PALBO + FULV demonstrated a statistically significant and clinically meaningful OS benefit compared with PBO + PALBO + FULV.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39236276/

Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine ... Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04191499

NCT04191499 | A Study Evaluating the Efficacy and Safety ... This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus ...

9. nejm.org nejm.org/doi/10.1056/NEJMoa2404625

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced ... Inavolisib plus palbociclib–fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib–fulvestrant, with a greater ...