Home Administration of Pertuzumab + Trastuzumab for Breast Cancer

(ProHer Trial)

Recruiting at 65 trial locations

Overseen By Reference Study ID Number: MO43110 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Corticosteroids, Live vaccines

Disqualifiers: Metastatic cancer, Serious cardiac illness, others

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

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

Compensation: Varies

Number of Visits: Unknown

347 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, pertuzumab and trastuzumab, given as an injection under the skin. It focuses on patients with a specific type of breast cancer. The goal is to see if patients prefer getting this treatment at home or in the hospital. These drugs work by attaching to a protein on cancer cells to stop them from growing. Pertuzumab was originally developed independently from trastuzumab and later found to work well together when combined with trastuzumab.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug for breast cancer?

The fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) was shown to be as effective as the intravenous version in maintaining drug levels and achieving similar complete response rates in patients with HER2-positive early breast cancer. Additionally, most patients preferred the subcutaneous version due to its quicker administration time. ^{1 2 3 4 5}

Is the combination of pertuzumab and trastuzumab safe for human use?

The combination of pertuzumab and trastuzumab, whether given intravenously or as a fixed-dose subcutaneous injection, has been studied for safety in patients with HER2-positive breast cancer. Serious side effects were similar between the subcutaneous and intravenous forms, and most patients preferred the subcutaneous method. Additionally, the combination with trastuzumab emtansine (T-DM1) showed no significant drug interaction issues, suggesting it is generally safe for human use. ^{1 2 4 6 7}

What makes the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection unique for breast cancer treatment?

This treatment is unique because it combines two drugs, pertuzumab and trastuzumab, into a single injection that can be given under the skin in just 5-8 minutes, compared to the traditional intravenous method that takes 1-2.5 hours. This makes it more convenient for patients and reduces the time and resource burden on healthcare facilities. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with early or locally advanced/inflammatory HER2-positive breast cancer. Participants must have completed neoadjuvant therapy and surgery, not be pregnant or breastfeeding, agree to use contraception, and have no severe allergies to study drugs. They should not have metastatic cancer, uncontrolled diseases, recent thromboembolism without stable anticoagulation treatment, a history of other malignancies within the last 5 years (except certain treated cancers), or any condition that would make it unsafe for them to participate.

Inclusion Criteria

You tested negative for hepatitis B surface antigen (HBsAg) at the screening.

I am fully active or can carry out light work.

I have been screened for hepatitis B with specific antibody results.

Exclusion Criteria

I have an active liver disease such as hepatitis or autoimmune disorder.

I have a history of irregular heartbeats or factors that increase my risk.

I have a high risk for breast cancer and have taken medication to lower my risk.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pertuzumab and trastuzumab with chemotherapy options for 6 to 8 cycles, each cycle lasting 3 weeks

18-24 weeks

Adjuvant Treatment

Participants receive PH FDC SC treatment in a cross-over period between hospital and home settings, followed by continuation to complete 18 cycles of HER2-directed therapy

up to 54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC)
• Pertuzumab IV
• Trastuzumab Emtansine
• Trastuzumab IV

Trial Overview The study tests patient preference for home versus hospital administration of a fixed-dose combination of Pertuzumab and Trastuzumab given subcutaneously after surgery in those with HER2-positive breast cancer. It also includes Investigator's Choice of Chemotherapy, IV forms of Pertuzumab and Trastuzumab, Trastuzumab Emtansine treatments along with necessary surgeries and radiotherapy.

Participant Groups

Group I: Arm E: Adjuvant Trastuzumab Emtansine Experimental Treatment 1 Intervention

Participants with pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy and surgery will enter Arm E to receive trastuzumab emtansine for 14 cycles. Trastuzumab emtansine will be administered IV in the hospital as per prescribing information.

Group II: Arm D: Adjuvant PH FDC SC at Home, Then in Hospital Experimental Treatment 1 Intervention

During the adjuvant phase, participants who have achieved pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital (run-in period). After completion of the last cycle of radiotherapy and the last cycle of PH FDC SC (run-in period), participants will then be randomized with a ratio of 1:1 into one of two treatment arms (Arm C or D) in a cross-over treatment period to receive the next 6 cycles of PH FDC SC treatment. Participants in Arm D will receive 3 cycles of PH FDC SC in the home setting and then 3 cycles of PH FDC SC in the hospital. After the cross-over treatment period, participants will receive the remaining PH FDC SC treatment cycles required to complete the planned 18 cycles of HER2-directed therapy, unless of disease recurrence, unacceptable toxicity, or withdrawal. Study treatment during this treatment continuation period will be administered either in the hospital or in the home setting as selected by the participant at the end of the crossover period.

Group III: Arm C: Adjuvant PH FDC SC in Hospital, Then at Home Experimental Treatment 1 Intervention

During the adjuvant phase, participants who have achieved pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital (run-in period). After completion of the last cycle of radiotherapy and the last cycle of PH FDC SC (run-in period), participants will then be randomized with a ratio of 1:1 into one of two treatment arms (Arm C or D) in a cross-over treatment period to receive the next 6 cycles of PH FDC SC treatment. Participants in Arm C will receive 3 cycles of PH FDC SC in the hospital and then 3 cycles of PH FDC SC in the home setting. After the cross-over treatment period, participants will receive the remaining PH FDC SC treatment cycles required to complete the planned 18 cycles of HER2-directed therapy, unless of disease recurrence, unacceptable toxicity, or withdrawal. Study treatment during this treatment continuation period will be administered either in the hospital or in the home setting as selected by the participant at the end of the crossover period.

Group IV: Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy Experimental Treatment 4 Interventions

During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with the fixed dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH FDC SC will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH FDC SC will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).

Group V: Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy Experimental Treatment 5 Interventions

During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with pertuzumab and trastuzumab intravenously (PH IV) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH IV will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH IV will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).

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

The novel fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PHESGO®) is non-inferior to the traditional intravenous (IV) administration in terms of drug levels and efficacy, with comparable total pathologic complete response rates (59.7% for PHESGO® vs 59.5% for IV).

PHESGO® can be administered in just 5-8 minutes, significantly reducing the time burden on patients and medical facilities compared to the 1-2.5 hours required for IV infusions, and 85% of patients preferred the subcutaneous option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach. DuMond, B., Patel, V., Gross, A., 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]

In a review of six studies involving 996 patients with HER2-positive breast cancer, the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane did not significantly improve objective response or clinical benefit rates compared to T-DM1 alone.

While the combination treatment was associated with increased risks of certain adverse events like diarrhea and rash, it also showed a decreased risk of thrombocytopenia, indicating a complex safety profile that requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. Zhang, J., Li, J., Zhu, C., et al.[2022]

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]

In T-DM1-resistant HER2-positive breast cancer cells, the combination of trastuzumab and pertuzumab (TRAS + PER) showed enhanced antitumor effects, significantly inhibiting cell proliferation and inducing apoptosis compared to either drug alone.

The study demonstrated that TRAS + PER effectively suppressed tumor growth in a xenograft model of T-DM1-resistant cancer, suggesting it could be a promising treatment option for patients who develop resistance to T-DM1 while maintaining HER2 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. Yamashita-Kashima, Y., Shu, S., Osada, M., et al.[2021]

References

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

Incidence and severity of anaphylaxis and hypersensitivity in trials of intravenous pertuzumab plus trastuzumab or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection for HER2-positive breast cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach. [2021]

3. 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]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. [2022]

5. 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]

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

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Drug interaction potential of trastuzumab emtansine (T-DM1) combined with pertuzumab in patients with HER2-positive metastatic breast cancer. [2019]