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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well trastuzumab and pertuzumab work in treating patients with HER2-amplified non-breast, non-gastric/gastroesophageal junction, and non-colorectal cancers. Pertuzumab and trastuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When pertuzumab or trastuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Trastuzumab is approved for the treatment of certain types of HER2-amplified cancers such as breast and gastric cancers. Research has shown that treatment with two anti-HER2 therapies in combination may be more effective at treating HER2-positive patients than giving one anti-HER2 therapy alone. Giving trastuzumab and pertuzumab in combination may be effective at treating patients with HER2-amplified cancers that aren't breast, gastric, or colorectal.

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.

What data supports the effectiveness of the drug combination of Trastuzumab and Pertuzumab for cancer?

Research shows that adding Pertuzumab to Trastuzumab and chemotherapy can help people with HER2-positive metastatic breast cancer live longer and slow down the disease's progression. In a large study, this combination increased the 3-year survival rate by 10% to 15% and extended the time patients lived without the cancer getting worse by about 6 months. ^{1 2 3 4 5}

What safety data exists for Trastuzumab and Pertuzumab in cancer treatment?

Pertuzumab, when used in combination with Trastuzumab, has been associated with side effects like diarrhea and rash. Diarrhea is common but not dose-limiting, while rash occurs in about 24.6% of patients, with a higher risk compared to those not receiving Pertuzumab. ^{6 7 8 9 10}

How is the drug combination of Trastuzumab and Pertuzumab unique for treating HER2-positive cancer?

The combination of Trastuzumab and Pertuzumab is unique because it targets different sites on the HER2 protein, providing a more comprehensive blockade of HER2 signaling, which can lead to better outcomes in HER2-positive cancers compared to using Trastuzumab alone. ^{1 2 3 5 11}

Research Team

Roisin M Connolly

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. England 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. [2021]

4. 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]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice. [2022]

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

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab-induced myasthenia gravis: A fatal case report. [2018]

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]