Inavolisib Combination for Breast Cancer

(INAVO120 Trial)

Recruiting at 302 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

325 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination (inavolisib, palbociclib, and fulvestrant) for patients with a specific type of advanced breast cancer that got worse after hormone therapy. The treatment aims to stop cancer cells from growing and spreading by attacking them in different ways.

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.

What data supports the effectiveness of the drug combination of Fulvestrant, Faslodex, Inavolisib, Itovebi, GDC-0077, Palbociclib, and Ibrance for breast cancer?

Research shows that combining palbociclib (Ibrance) with fulvestrant (Faslodex) significantly improves progression-free survival (the time during which the cancer does not get worse) in women with hormone receptor-positive, HER2-negative advanced breast cancer compared to fulvestrant alone. ^{1 2 3 4 5}

Is the combination of Inavolisib and other drugs like Fulvestrant and Palbociclib safe for treating breast cancer?

The combination of Palbociclib (Ibrance) and Fulvestrant (Faslodex) has been studied for safety in treating advanced breast cancer. Common side effects include low white blood cell counts, infections, tiredness, nausea, anemia (low red blood cell count), mouth sores, headache, diarrhea, and low platelet counts. ^{1 3 5 6 7}

What makes the Inavolisib Combination for Breast Cancer unique?

The Inavolisib Combination for Breast Cancer is unique because it includes inavolisib (GDC-0077), a novel component not commonly used in standard treatments, alongside palbociclib and fulvestrant, which are already known to improve outcomes in hormone receptor-positive, HER2-negative metastatic breast cancer. This combination may offer a new approach by potentially enhancing the effectiveness of existing therapies. ^{1 2 5 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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.

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

Findings from Research

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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

2. England 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). [2022]

3. England 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. [2023]

4. Japan 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. [2020]

5. England 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. [2022]

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

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Palbociclib in combination with fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: PALOMA-3 subgroup analysis of Japanese patients. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [2022]