Pertuzumab + Trastuzumab for HER2-Positive Breast Cancer

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Nursing, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if PET scans (a type of imaging) can predict the response of patients with HER2-positive breast cancer to a treatment combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) before surgery. The focus is on patients with untreated HER2-positive breast cancer in specific stages of progression. Ideal candidates for this trial have HER2-positive breast cancer that has not spread to distant body parts. As a Phase 2 trial, the study measures the treatment's effectiveness in an initial, smaller group, providing valuable insights into its potential success.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using investigational agents or have received certain treatments for breast cancer, you may need to stop those before participating.

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

Research has shown that patients generally tolerate the combination of pertuzumab and trastuzumab well. One study found that the risk of serious side effects remained similar across various treatment combinations involving these two drugs. The most common side effects were manageable, and the treatment demonstrated benefits over time. Another long-term study found that adding pertuzumab to trastuzumab, along with chemotherapy, reduced the risk of death by 17% over ten years.

Although these treatments are approved for certain conditions, discussing potential side effects and the best options with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using pertuzumab and trastuzumab together for HER2-positive breast cancer because they target the cancer cells in a unique way. Unlike other treatments that might focus on a single pathway, this combination blocks the HER2 protein from two different angles, potentially stopping cancer growth more effectively. Additionally, this dual approach is designed to be used preoperatively, which could shrink tumors more effectively before surgery. This combination therapy could offer a more powerful option for tackling aggressive breast cancer types.

What evidence suggests that this trial's treatments could be effective for HER2-positive breast cancer?

Research has shown that using pertuzumab and trastuzumab together effectively treats HER2-positive breast cancer. In this trial, participants will receive preoperative treatment with both drugs. Studies have found that adding pertuzumab to trastuzumab and chemotherapy can lower the risk of death by 17% over ten years. Specifically, one study found that patients using this combination had a 32% lower risk of death compared to those using a placebo with trastuzumab and docetaxel. This combination has also been linked to an average survival time of 57.1 months in some patients. These findings suggest that the pertuzumab and trastuzumab combination can significantly improve outcomes for people with this type of breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Roisin Connolly, MBBCh

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for adults with untreated breast cancer that's not yet spread elsewhere (stages T2, T3, or T4a-c), who are willing to use non-hormonal contraception if they can have children. They must be able to undergo PET scans and biopsies, have a certain type of tumor (HER2-positive and low hormone receptor levels), and their body should be functioning well overall.

Inclusion Criteria

AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 2 times the upper limit of normal

Hemoglobin ≥ 10 g/dL

I am fully active or can carry out light work.

Exclusion Criteria

I've had treatment for my current breast cancer but stopped any preventive medication at least a month ago.

I am not pregnant or nursing.

I am not currently using any experimental drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Preoperative treatment with trastuzumab and pertuzumab for 12 weeks, assessed by PET

12 weeks

4 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pertuzumab
• Positron Emission Tomography (PET)
• Trastuzumab

Trial Overview

The study tests whether early changes seen on PET scans can predict the success of pre-surgery treatment with trastuzumab and pertuzumab in patients with HER2-positive breast cancer. It aims to see if these imaging changes correlate with how well the tumors respond.

How Is the Trial Designed?

Group I: Trastuzumab and Pertuzumab Experimental Treatment 3 Interventions

Preoperative treatment with trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV) and pertuzumab (840 mg as a loading dose, then 420 mg every 3 weeks, IV) every 3 weeks for 4 doses (total 12 weeks or 3 months of treatment) as assessed by Positron Emission Tomography (PET)

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

Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Pertuzumab is an effective anti-HER2 monoclonal antibody that works by preventing HER2 from forming heterodimers, which reduces tumor cell growth and survival, particularly in HER2-positive metastatic breast cancer.

In the phase III CLEOPATRA trial involving a combination of pertuzumab, trastuzumab, and docetaxel, patients experienced significantly improved progression-free survival and overall survival compared to those receiving placebo, with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. McCormack, PL.[2021]

The novel anti-HER2 antibody 5G9 showed significantly stronger synergistic effects with trastuzumab in inhibiting cell growth compared to pertuzumab, achieving an 85% inhibition rate versus 55% (P<0.001).

In animal models, the combination of 5G9 and trastuzumab demonstrated greater antitumor efficacy than the pertuzumab and trastuzumab combination, suggesting that 5G9 could be a more effective treatment option for HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel HER2-targeting antibody 5G9 identified by large-scale trastuzumab-based screening exhibits potent synergistic antitumor activity. Ding, X., Gu, W., Zhong, Y., et al.[2021]

In a phase 2 trial involving 30 patients with relapsed follicular lymphoma, the combination of pembrolizumab and rituximab showed a promising overall response rate of 67% and a complete response rate of 50%.

The treatment demonstrated a favorable safety profile, with most adverse events being low-grade; however, 20% of patients discontinued due to treatment-related adverse effects, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Nastoupil, LJ., Chin, CK., Westin, JR., et al.[2022]

Pertuzumab, a new monoclonal antibody targeting HER2, has shown improved patient outcomes in clinical trials for early-stage and metastatic HER2-positive breast cancer, especially when used in combination with chemotherapy and trastuzumab.

The review highlights that while trastuzumab has improved survival for HER2-positive breast cancer, there is still a need for better treatment options, which pertuzumab aims to address, particularly for patients who continue to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. Lamond, NW., Younis, T.[2021]

In a phase 3 trial involving 780 patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer, adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival compared to placebo, with median survival times of 17.5 months for the pertuzumab group and 14.2 months for the control group.

While serious adverse events were more common in the pertuzumab group (45%) compared to the control group (39%), no treatment-related deaths occurred in the pertuzumab group, suggesting a safety profile that warrants further investigation despite the lack of survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Tabernero, J., Hoff, PM., Shen, L., et al.[2023]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

In a study of 133 patients treated with alemtuzumab (ALZ), 6.02% developed long-term autoimmune skin disorders, including conditions like alopecia areata and vitiligo, indicating a notable risk of skin-related adverse events post-treatment.

The autoimmune skin reactions are likely linked to immune dysregulation caused by ALZ, suggesting that ongoing monitoring for these conditions is important for patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin Autoimmunity Secondary to Alemtuzumab in a Tertiary Care Spanish Hospital. López Ruiz, R., Sánchez Fernández, F., Ruiz de Arcos, M., et al.[2023]

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Immature efficacy data showed high event-free rates, consistent with the known clinical benefit of pertuzumab and trastuzumab (although follow-up was relatively ...

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clinical-breast-cancer.com

clinical-breast-cancer.com/article/S1526-8209(25)00107-7/fulltext

Long-Term Safety and Efficacy of the Fixed-Dose ...

Immature efficacy data showed high event-free rates, consistent with the known clinical benefit of pertuzumab and trastuzumab (although follow-up was ...