Trastuzumab + Pertuzumab for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-HER2 therapies

Disqualifiers: Breast cancer, Gastric cancer, Colorectal cancer, Hypersensitivity to trastuzumab, 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: 5

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two drugs, trastuzumab and pertuzumab, in treating certain HER2-amplified cancers. These drugs target the HER2 protein on some cancer cells, blocking signals that promote cell growth. The trial seeks to determine if these drugs can effectively treat HER2-positive cancers that are not breast, gastric, or colorectal. Patients with HER2-amplified cancer, excluding those in the breast, stomach, or colon, who have not previously received similar treatments, may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering patients a chance to benefit from potentially effective therapies.

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 coordinators or your doctor.

Is there any evidence suggesting that trastuzumab and pertuzumab are likely to be safe for humans?

Research has shown that combining trastuzumab and pertuzumab is safe and effective in treating HER2-positive cancers, yielding promising results. Specifically, using these two drugs together significantly decreased the risk of cancer progression or death in some patients.

However, possible side effects should be considered. In some studies, over 60% of patients experienced serious side effects, including tiredness, nausea, and more severe issues like heart problems. Notably, trastuzumab is already approved for treating certain cancers, such as breast cancer, indicating its established safety for human use.

While these findings are encouraging, joining a clinical trial is a personal decision. Discuss the potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of trastuzumab and pertuzumab for treating certain cancers because these drugs target cancer cells in a unique way. Unlike standard treatments that might broadly attack cancer cells, these drugs specifically block the HER2 protein, which is found in excess on some cancer cells and helps them grow. By combining trastuzumab and pertuzumab, this treatment can potentially offer a more precise attack on cancer cells, reducing harm to healthy cells and possibly enhancing effectiveness. Moreover, the combination could improve outcomes for patients whose cancers are resistant to other therapies, offering new hope for more effective management of their condition.

What evidence suggests that trastuzumab and pertuzumab might be effective treatments for HER2-amplified cancers?

This trial will evaluate the combination of trastuzumab and pertuzumab for treating certain HER2-positive cancers. Studies have shown that using trastuzumab and pertuzumab together can effectively slow cancer growth and extend patient survival. For example, one study found that these drugs, when combined with chemotherapy, reduced the risk of death by 32% in HER2-positive cancers. Another study demonstrated a 17% reduction in the risk of death in early-stage HER2-positive breast cancer. These findings suggest that trastuzumab and pertuzumab could benefit patients with other types of HER2-positive cancers by inhibiting cancer cell growth and aiding the immune system in attacking them. ^{1 2 3 5 6}

Who Is on the Research Team?

Roisin M Connolly

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with non-breast, non-gastric/gastroesophageal junction, and non-colorectal cancers that have high levels of the HER2 gene. Participants must not have heart issues as shown by recent ECGs or echocardiograms, no known allergies to trastuzumab or pertuzumab, and cannot have had previous anti-HER2 therapies. Women who can become pregnant and men with partners of childbearing potential must agree to use contraception.

Inclusion Criteria

My recent ECG showed no significant heart issues.

I have never been treated with HER2-targeting drugs.

I agree to use effective birth control or abstain from sex during and for 7 months after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pertuzumab and trastuzumab intravenously every 3 weeks

Up to 3 years

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Pertuzumab
• Trastuzumab

Trial Overview The study tests a combination of two monoclonal antibodies—trastuzumab and pertuzumab—on patients with HER2-amplified cancers (excluding breast, gastric/gastroesophageal junction, and colorectal). These drugs block growth signals in cancer cells by attaching to the HER2 protein on their surface which may also mark them for destruction by the immune system.

How Is the Trial Designed?

Group I: Treatment (pertuzumab, trastuzumab) Experimental Treatment 6 Interventions

Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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, a monoclonal antibody targeting HER2, significantly improves progression-free survival in patients with HER2-positive metastatic breast cancer, with a median of 18.5 months compared to 12.4 months for the placebo group, based on a phase III trial with previously untreated patients.

While the overall safety profile of pertuzumab is similar to placebo, it is associated with a higher incidence of specific side effects such as diarrhea, rash, and neutropenia, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Boix-Perales, H., Borregaard, J., Jensen, KB., et al.[2023]

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]

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]

In a phase IIa study involving 30 patients with advanced gastric cancer, the combination of pertuzumab and trastuzumab showed a well-tolerated safety profile, with partial responses in 86% of patients receiving a specific dosing regimen.

The pharmacokinetics indicated that the serum concentration of pertuzumab was lower in this gastric cancer population compared to those with metastatic breast cancer, leading to the selection of the 840 mg q3w dose for further phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Kang, YK., Rha, SY., Tassone, P., et al.[2021]

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]

Pembrolizumab, an immune checkpoint inhibitor, can enhance immune responses against cancer but is associated with serious immune-related adverse events (irAEs), including a rare case of fatal myasthenia gravis in a 63-year-old male patient.

This case emphasizes the importance of recognizing symptoms of irAEs early and discontinuing pembrolizumab to potentially improve patient outcomes, as the patient ultimately succumbed to acute respiratory failure despite aggressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced myasthenia gravis: A fatal case report. March, KL., Samarin, MJ., Sodhi, A., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41160818/

Trastuzumab Deruxtecan plus Pertuzumab for HER2- ... Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment ...

2. roche.com roche.com/media/releases/med-cor-2025-05-13

Ten-year APHINITY data show Roche's Perjeta-based ... After ten years, the risk of death was reduced by 17% for people treated with Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy (the Perjeta- ...

3. perjeta-hcp.com perjeta-hcp.com/metastatic/efficacy.html

PERJETA® (pertuzumab) for HER2+ Metastatic Outcomes | HCP 32% reduction in the risk of death vs placebo + Herceptin + docetaxel · Median follow-up was 49.5 months in the PERJETA-treated group and 50.6 months in the ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2789454

Comparative Effectiveness and Safety of Pertuzumab ... End-of-study analyses of the CLEOPATRA trial found median overall survival (OS) of 57.1 months in patients receiving pertuzumab compared with ...

5. onclive.com onclive.com/view/adjuvant-pertuzumab-plus-trastuzumab-and-chemotherapy-leads-to-os-benefit-in-early-stage-her2-breast-cancer

Adjuvant Pertuzumab Plus Trastuzumab and ... - OncLive The APHINITY trial showed a 17% reduction in death risk with pertuzumab in early-stage HER2-positive breast cancer. The 10-year overall survival ...

6. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-plus-pertuzumab-reduced-the-risk-of-disease-progression-or-death-by-44-percent-vs-THP-as-1st-line-therapy-in-patients-with-HER2-positive-metastatic-breast-cancer-in-DESTINY-Breast09-Phase-III-trial.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus ... ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% vs. THP as 1st-line therapy ...