Inavolisib + Phesgo for Breast Cancer

(INAVO122 Trial)

Recruiting at 231 trial locations

Overseen By Reference Study ID Number: WO44263 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: PI3K inhibitors, AKT inhibitors

Disqualifiers: Diabetes, Liver disease, Lung disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called inavolisib combined with Phesgo, which includes three existing drugs. It targets patients with untreated HER2-positive advanced breast cancer. Inavolisib works by blocking growth signals in cancer cells, while Phesgo targets a protein on these cells to stop their growth and spread.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on medications for Type 2 diabetes or have a history of certain conditions like liver disease or lung disease, you may not be eligible to participate.

Is the combination of Inavolisib and Phesgo safe for human use?

Phesgo, a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf, has been approved for use in HER2-positive breast cancer and is generally considered safe, with common side effects including hair loss, nausea, diarrhea, anemia (low red blood cell count), and weakness. Trastuzumab, part of Phesgo, has been used safely in self-administered injections without toxicity. However, specific safety data for Inavolisib in combination with Phesgo is not provided in the available research. ^{1 2 3 4 5}

What makes the drug Inavolisib + Phesgo unique for breast cancer treatment?

The drug Phesgo, which combines pertuzumab, trastuzumab, and hyaluronidase-zzxf, is unique because it is administered as a subcutaneous injection (under the skin) rather than the traditional intravenous (IV) infusion, making it more convenient and less time-consuming for patients with HER2-positive breast cancer. ^{1 6 7 8 9}

What data supports the effectiveness of the drug Inavolisib + Phesgo for breast cancer?

The FDA approved Phesgo, a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf, for treating HER2-positive breast cancer based on studies showing it works as well as the intravenous versions of these drugs. This approval suggests that the subcutaneous form is effective for breast cancer treatment. ^{1 2 8 9 10}

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 HER2-positive advanced breast cancer that hasn't been treated yet. They should have a certain gene mutation (PIK3CA), good heart function, and no diabetes requiring systemic treatment. People who've had specific eye conditions, severe liver disease, lung problems like pneumonitis, or inflammatory bowel disease can't join.

Inclusion Criteria

My cancer is confirmed HER2 positive by a specialized lab test.

My cancer has a PIK3CA mutation according to a specialized test.

I am fully active or can carry out light work.

Exclusion Criteria

I have had treatments for advanced HER2-positive breast cancer before starting the current therapy.

I have or had inflammatory bowel disease.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive Phesgo plus Taxane-Based Chemotherapy

6-12 weeks

Maintenance Therapy

Participants receive Inavolisib plus Phesgo or Placebo plus Phesgo

21-day cycles, ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-day safety follow-up, then every 6 months up to 111 months

What Are the Treatments Tested in This Trial?

Interventions

• Inavolisib
• Phesgo

Trial Overview The study tests the safety and effectiveness of Inavolisib combined with Phesgo against a placebo with Phesgo after initial therapy. It's for those whose breast cancer has spread or can't be surgically removed.

How Is the Trial Designed?

Group I: Maintenance Therapy: Inavolisib plus Phesgo Experimental Treatment 3 Interventions

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

Group II: Induction Therapy: Phesgo plus Taxane-Based Chemotherapy Experimental Treatment 2 Interventions

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

Group III: Maintenance Therapy: Placebo plus Phesgo Active Control 3 Interventions

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

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

Approved in United States as Phesgo for:

• HER2-positive breast cancer

Approved in European Union as Phesgo for:

• HER2-positive 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 a study involving 160 patients with HER2-positive early breast cancer, 85% preferred the subcutaneous (SC) injection of the fixed-dose combination of pertuzumab and trastuzumab (PH FDC SC) over intravenous (IV) infusion, mainly due to reduced clinic time and greater comfort during administration.

PH FDC SC was well tolerated with low rates of serious adverse events, and patient satisfaction was significantly higher with SC injections (88.1% satisfied) compared to IV infusions (67.5% satisfied), indicating it is a safer and more convenient treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. O'Shaughnessy, J., Sousa, S., Cruz, J., et al.[2021]

Subcutaneous (SC) administration of the fixed-dose combination of pertuzumab and trastuzumab (PH FDC SC) for HER2-positive breast cancer shows significant time and resource savings compared to traditional intravenous (IV) administration, as evidenced by a systematic review of 72 studies.

The majority of studies indicated that SC administration not only reduces the time required for preparation and administration but also leads to cost savings by decreasing the healthcare professional time and resources needed, making it a more efficient option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Time and Resource Use Costs of Subcutaneous Versus Intravenous Administration of Oncology Biologics in a Hospital Setting. McCloskey, C., Ortega, MT., Nair, S., et al.[2023]

The FDA approved Phesgo, a subcutaneous injection combining pertuzumab, trastuzumab, and hyaluronidase-zzxf, for treating HER2-positive early-stage and metastatic breast cancer, based on the FeDeriCa trial which showed that the subcutaneous formulation is pharmacokinetically comparable to the intravenous versions.

The study demonstrated that the subcutaneous treatment had similar efficacy to intravenous treatments, with common side effects including alopecia, nausea, and diarrhea, supporting its use across all approved indications for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. Gao, JJ., Osgood, CL., Gong, Y., et al.[2022]

The subcutaneous formulation of trastuzumab demonstrated a non-inferior pharmacokinetic profile and efficacy compared to the intravenous formulation in patients with HER2-positive early breast cancer, with similar serum drug levels and pathological complete response rates.

While the overall safety profile was comparable, the subcutaneous group experienced a higher incidence of serious adverse events, particularly infections, suggesting careful monitoring may be needed for this administration route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Ismael, G., Hegg, R., Muehlbauer, S., et al.[2022]

A meta-analysis of individual patient data from 6 randomized controlled trials involving 2971 participants indicated a higher incidence of serious and high-grade infections with subcutaneous administration of trastuzumab and rituximab compared to intravenous administration, although initial results were not statistically significant.

After excluding an outlier study, the risk of serious infections became statistically significant, suggesting that clinical surveillance may be necessary when switching to subcutaneous administration due to the increased infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infective complications in cancer patients treated with subcutaneous versus intravenous trastuzumab and rituximab: An individual patient data meta-analysis. Alexander, M., Jachno, K., Phillips, KA., et al.[2023]

The pharmacokinetics of subcutaneous (SC) pertuzumab in the fixed-dose combination (PH FDC SC) was effectively modeled, showing that it has a similar efficacy and safety profile to intravenous pertuzumab, based on population pharmacokinetic modeling of data from the FeDeriCa study.

There was no significant impact of pertuzumab on the pharmacokinetics of trastuzumab, and higher levels of pertuzumab did not correlate with increased adverse events or improved treatment response, supporting the safety of the approved dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exploratory exposure-response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study. Wang, B., Deng, R., Hennig, S., et al.[2022]

In a study of 266 patients with HER2-positive metastatic breast cancer, the majority received a treatment regimen of trastuzumab, pertuzumab, and a taxane, which aligns with the standard first-line therapy.

The median progression-free survival (PFS) for patients was 16.9 months, and the safety profile, including common side effects like fatigue and diarrhea, was consistent with findings from the pivotal CLEOPATRA trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes. Robert, NJ., Goertz, HP., Chopra, P., et al.[2020]

A case report highlights that self-administration of subcutaneous trastuzumab is feasible and safe, showing no toxicity in the patient involved.

The authors suggest that relaxing regulations on the availability of subcutaneous trastuzumab could lead to more affordable treatment options for patients, promoting self-administration as a viable alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous auto-administration of trastuzumab following therapeutic education: A case report. Deppenweiler, M., Debled, M., Robquin, JL., et al.[2019]

Adding pertuzumab to trastuzumab and docetaxel for treating HER2+ metastatic breast cancer did not significantly increase patient survival, while the treatment costs were substantially higher (€163,360 compared to €90,112 per patient).

The incremental cost-effectiveness ratio of €87,200 per quality-adjusted life-year far exceeds the acceptable threshold of €46,500, indicating that pertuzumab is not cost-effective in the Czech healthcare context, although the short follow-up period (mean of 20-21 months) may have influenced these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cost-Effectiveness of Pertuzumab for the Treatment of Metastatic HER2+ Breast Cancer in Czechia: A Semi-Markov Model Using Cost States. Šlegerová, L., Kopečková, K.[2023]

In a case series of 19 patients with previously treated HER2-positive metastatic breast cancer, the combination of pertuzumab, trastuzumab, and taxane therapy resulted in a median progression-free survival of 4.1 months.

The treatment was associated with minimal adverse effects, showing only a slight decrease in left ventricular ejection fraction (-1%) and no occurrences of neutropenic fever, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination pertuzumab, trastuzumab, and taxane for metastatic breast cancer after first progression: a single institution's experience. Dao, BD., Ho, H., Quintal, LN.[2016]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review of Time and Resource Use Costs of Subcutaneous Versus Intravenous Administration of Oncology Biologics in a Hospital Setting. [2023]

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

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. [2022]

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

Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Infective complications in cancer patients treated with subcutaneous versus intravenous trastuzumab and rituximab: An individual patient data meta-analysis. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exploratory exposure-response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes. [2020]

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

Subcutaneous auto-administration of trastuzumab following therapeutic education: A case report. [2019]

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

The Cost-Effectiveness of Pertuzumab for the Treatment of Metastatic HER2+ Breast Cancer in Czechia: A Semi-Markov Model Using Cost States. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Combination pertuzumab, trastuzumab, and taxane for metastatic breast cancer after first progression: a single institution's experience. [2016]