Pertuzumab + Trastuzumab for HER2-Positive Breast Cancer

Recruiting at 9 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

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research is being done to determine if early changes on a type of imaging procedure called PET (Positron Emission Tomography) can predict which patients are most likely to respond to the combination of trastuzumab and pertuzumab when given prior to surgery.

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.

What are the safety concerns for Pertuzumab and Trastuzumab in treating HER2-Positive Breast Cancer?

Pertuzumab, when used in combination with Trastuzumab, has been associated with a risk of developing a rash, which varies depending on the type of cancer being treated. In clinical trials, about 24.6% of patients experienced some form of rash, but severe cases were rare, occurring in about 1.1% of patients. ^{1 2 3 4 5}

What makes the drug combination of Pertuzumab and Trastuzumab unique for treating HER2-positive breast cancer?

The combination of Pertuzumab and Trastuzumab is unique because they target different sites on the HER2 receptor, working together to more effectively inhibit cancer cell growth. This combination has been shown to improve survival rates in patients with HER2-positive metastatic breast cancer compared to using Trastuzumab alone. ^{6 7 8 9 10}

What evidence supports the effectiveness of the drug combination Pertuzumab and Trastuzumab for HER2-positive breast cancer?

Research shows that adding Pertuzumab to Trastuzumab and chemotherapy improves survival rates in patients with HER2-positive breast cancer. Studies have demonstrated that this combination increases overall survival and progression-free survival, meaning patients live longer and their cancer takes longer to worsen. ^{7 8 9 11 12}

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 haven't had cancer treatment in the last 5 years, except for specific skin or cervical cancers.

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, 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]

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]

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]

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]

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]

Citations

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

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

2. England 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. [2023]

3. France pubmed.ncbi.nlm.nih.gov

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

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

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. [2022]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Related Side Effects: Acute Renal Failure and Severe Neurological Toxicity. [2022]

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

Risk of rash with the anti-HER2 dimerization antibody pertuzumab: a meta-analysis. [2016]

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

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]

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

Skin Autoimmunity Secondary to Alemtuzumab in a Tertiary Care Spanish Hospital. [2023]

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

Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. [2022]

11. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of late line pertuzumab with trastuzumab and chemotherapy in HER2-positive metastatic breast cancer: An Australian case series. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A novel HER2-targeting antibody 5G9 identified by large-scale trastuzumab-based screening exhibits potent synergistic antitumor activity. [2021]