PHESGO Maintenance for Breast Cancer

(DEMETHER Trial)

Recruiting at 22 trial locations

Overseen By MEDSIR

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: MedSIR

Must not be taking: Anticonvulsants, Steroids, others

Disqualifiers: CNS metastases, Cardiac disease, 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: 12

165 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

DEMETHER is a phase II trial exploring the maintenance of trastuzumab and pertuzumab fixed dose combination (FDC) for subcutaneous administration (SC, PHESGO) following trastuzumab deruxtecan (T-DXd) as induction treatment for HER2-positive unresectable locally recurrent or metastatic breast cancer (MBC) patients.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently in another therapeutic clinical trial or have received cancer therapy within 14 days before starting the study drugs.

Is PHESGO (Pertuzumab and Trastuzumab) generally safe for humans?

The research articles provided do not contain specific safety data for PHESGO (Pertuzumab and Trastuzumab) or its components. Therefore, no relevant safety information is available from these sources. ^{1 2 3 4 5}

How is the drug PHESGO unique for treating HER2-positive breast cancer?

PHESGO is unique because it combines pertuzumab and trastuzumab into a single subcutaneous injection, which can be administered 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 strain on medical centers. ^{6 7 8 9 10}

What data supports the effectiveness of the drug PHESGO (Pertuzumab and Trastuzumab) for breast cancer?

Research shows that combining pertuzumab with trastuzumab and chemotherapy improves survival in HER2-positive early and metastatic breast cancer. The CLEOPATRA study found that this combination significantly increases the time patients live without the cancer getting worse and overall survival. ^{6 9 11 12 13}

Who Is on the Research Team?

Javier Cortés, MD, PhD

Principal Investigator

Institute of Breast Cancer, Quirón Group, Barcelona (Spain)

Antonio Llombart-Cussac, MD

Principal Investigator

Arnau de Vilanova Hospital, Valencia (Spain)

José M Pérez-García, MD

Principal Investigator

International Breast Cancer Center (Spain)

Are You a Good Fit for This Trial?

This trial is for adults with HER2+ unresectable locally recurrent or metastatic breast cancer who haven't had chemo or HER2-targeted therapy for advanced disease. They should have a life expectancy of at least 12 weeks, be in good physical condition (ECOG 0-1), and able to provide tumor tissue samples. No prior chemotherapy for advanced disease is allowed.

Inclusion Criteria

My cancer is HER2 positive, confirmed by a lab test.

You are expected to live for at least 12 more weeks from the time of screening.

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive a 6-cycle induction phase with T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on day 1 of each 21-day cycle

18 weeks

6 visits (in-person)

Maintenance Treatment

Participants receive PHESGO with a loading dose followed by maintenance doses every 21 days

Up to 36 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival and subsequent anticancer therapy information collected every 3 months

Until end of study or participant withdrawal

Every 3 months (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pertuzumab
• Trastuzumab

Trial Overview The DEMETHER phase II trial tests maintenance treatment with PHESGO—a fixed dose combo of trastuzumab and pertuzumab—after initial treatment with trastuzumab deruxtecan (T-DXd) for specific breast cancer patients. The goal is to see how well the maintenance therapy works after the induction treatment.

How Is the Trial Designed?

Group I: T-DXd induction treatment phase followed by PHESGO maintenance treatment phase Experimental Treatment 3 Interventions

All patients will receive a 6-cycle induction phase with T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on day 1 (D1) of each 21-day cycle (Q3W). Participants may continue with PHESGO if T-DXd is discontinued prematurely due to unacceptable toxicity prior to disease progression and following recovering to Grade ≤ 1 toxicity, to Grade 0 in case of ILD/pneumonitis, or to Grade 2 for alopecia/other toxicities not considered a safety risk. If any T-DXd unacceptable toxicity occurs during the first 6 cycles of induction phase with T-DXd, participants may receive taxane-based chemotherapy concomitantly with PHESGO treatment at the discretion of the investigator. During the maintenance phase, all participants will receive PHESGO with a loading dose of 1200 mg pertuzumab/600 mg trastuzumab as a SC injection for 8 minutes on D1 of the first 21-day cycle, and with a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab as a SC Q3W.

Who Is Running the Clinical Trial?

MedSIR

Lead Sponsor

Trials

52

Recruited

24,300+

Hoffmann-La Roche

Industry 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

Published Research Related to This Trial

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 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]

In a study involving 11 patients with HER2-positive metastatic breast cancer who had previously progressed on trastuzumab therapy, the combination of trastuzumab and pertuzumab showed an objective response rate of 18%, indicating potential clinical benefit for selected patients.

Cardiac toxicity was observed in some patients, with left ventricular systolic dysfunction noted in six individuals, highlighting the need for careful cardiac monitoring during treatment despite most cases being asymptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. Portera, CC., Walshe, JM., Rosing, DR., et al.[2022]

The CLEOPATRA study found that adding pertuzumab to trastuzumab and docetaxel does not negatively affect health-related quality of life (HRQoL) in patients with HER2-positive metastatic breast cancer, with similar times to deterioration in physical and functional well-being between the treatment and placebo groups.

However, pertuzumab was associated with a significant delay in the worsening of breast cancer-specific symptoms, extending the median time to deterioration in the Breast Cancer Subscale score compared to placebo (26.7 weeks vs. 18.3 weeks).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Cortés, J., Baselga, J., Im, YH., et al.[2022]

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]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., 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 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]

In a study of 97 non-small cell lung cancer patients treated with pembrolizumab, 40% experienced treatment-related adverse events (trAEs), with common ones being rash, fatigue, and hypothyroidism.

Patients who experienced trAEs had significantly better clinical outcomes, including a higher objective response rate (38.5% vs. 8.9%), longer progression-free survival (248 days vs. 60 days), and longer overall survival (493 days vs. 144.5 days), suggesting that trAEs may be indicative of a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Lisberg, A., Tucker, DA., Goldman, JW., et al.[2022]

In a study of 25 patients with advanced ER+/HER2- breast cancer, pembrolizumab showed a modest overall response rate of 12% and a clinical benefit rate of 20%, indicating some effectiveness in this difficult-to-treat population.

The treatment was well tolerated, with 64% of patients experiencing treatment-related adverse events, primarily mild nausea and fatigue, and no treatment-related discontinuations or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Rugo, HS., Delord, JP., Im, SA., et al.[2022]

The FDA approved Phesgo, a subcutaneous injection combining pertuzumab, trastuzumab, and hyaluronidase-zzxf, for treating HER2-positive early-stage and metastatic breast cancer, based on the FeDeriCa trial which showed that the subcutaneous formulation is pharmacokinetically comparable to the intravenous versions.

The study demonstrated that the subcutaneous treatment had similar efficacy to intravenous treatments, with common side effects including alopecia, nausea, and diarrhea, supporting its use across all approved indications for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. Gao, JJ., Osgood, CL., Gong, Y., et al.[2022]

The PUFFIN study demonstrated that pertuzumab combined with trastuzumab and docetaxel significantly improved progression-free survival (PFS) in patients with HER2-positive breast cancer, with a median PFS of 14.5 months compared to 12.4 months for the placebo group, indicating strong efficacy consistent with previous studies.

Safety profiles were similar between the treatment and placebo groups, with no reported cases of heart failure, supporting the favorable safety profile of pertuzumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Xu, B., Li, W., Zhang, Q., et al.[2021]

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]

Citations

1. 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]

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

Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

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

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. [2023]

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

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

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

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

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

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. [2022]

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

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. [2022]

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

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. [2022]

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

Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. [2021]

13. 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]