PHESGO Maintenance for Breast Cancer
(DEMETHER Trial)
Recruiting in Palo Alto (17 mi)
+22 other locations
Overseen byJavier Cortés, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: MedSIR
Must not be taking: Anticonvulsants, Steroids, others
Disqualifiers: CNS metastases, Cardiac disease, others
No Placebo Group
Prior Safety Data
Trial Summary
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.
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.
12345Is 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.
678910How 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.
15111213Eligibility Criteria
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.
+7 more
Trial Timeline
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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: T-DXd induction treatment phase followed by PHESGO maintenance treatment phaseExperimental Treatment3 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwell HealthNew York, NY
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Who Is Running the Clinical Trial?
MedSIRLead Sponsor
Hoffmann-La RocheIndustry Sponsor
References
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]The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112).
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]Adding pertuzumab to trastuzumab and chemotherapy improves survival in HER2-positive early breast cancer and metastatic breast cancer. We assessed the efficacy and safety of pertuzumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic gastric or gastro-oesophageal junction cancer.
Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. [2022]To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy.
Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. [2022]The phase III CLEOPATRA study demonstrated that combining pertuzumab with trastuzumab plus docetaxel significantly improves progression-free and overall survival in previously untreated HER2-positive metastatic breast cancer. Here, we report health-related quality-of-life (HRQoL) results from CLEOPATRA.
Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]Adding trastuzumab to chemotherapy can prolong overall survival among women with metastatic or locally recurrent unresectable breast cancer that overexpresses HER-2 protein. Pertuzumab (Perjeta, Roche) is a monoclonal antibody that targets HER-2. It has a different binding site from that of trastuzumab, another anti-HER-2 antibody. Pertuzumab has been authorised in the European Union as an adjunct to the trastuzumab + docetaxel combination. A double-blind randomised placebo-controlled trial involving 808 carefully selected patients (including two men), followed for about 2.5 years, showed that the addition of pertuzumab to trastuzumab + docetaxel prolonged overall survival: it was estimated that the 3-year survival rate increased by 10% to 15%. Median progression-free survival was 6 months longer in the pertuzumab group. Addition of pertuzumab did not aggravate cardiac toxicity among patients with a low cardiovascular risk at baseline. In contrast, adding pertuzumab increased the incidence of potentially severe diarrhoea, mucocutaneous disorders (rash, dry skin, mucosal inflammation) and febrile neutropenia. In practice, these results are interesting but they must be confirmed in other comparative trials before recommending routine use of pertuzumab.
An unusual case of checkpoint-inhibitor-induced pleuropericarditis. [2023]Pembrolizumab is an immune checkpoint inhibitor that promotes effector T-cell functions on malignant cells by binding to programmed cell death protein 1 (PD-1). Pembrolizumab is well tolerated in most cases with an adverse event profile consisting mainly of pruritus, fatigue, and anorexia. Cardiotoxicity comprises 1% of the total adverse events.
Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]Aim: Reporting toxicities of targeted therapies (TTs) and immunotherapy in oncology requires special attention. Materials & methods: We identified TTs and immunotherapies approved by the US FDA for solid malignancies in the adult population. Publications were reviewed according to a 24-point score based on the Consolidated Standards of Reporting Trials guidance. Results: We identified 81 trials (>45,000 patients). The experimental drug was studied as single agent in 51% of the cases; setting of disease was mainly (95%) advanced/metastatic. Lowest scores in adverse event (AE) description regarded: reporting recurrent/late toxicities and duration of the AEs (>90%), time of occurrence and indication of all-grade AEs (>75%). Conclusion: Suboptimal reporting of AEs in trials leading to approval of TTs and immunotherapy was shown. Improving AE descriptions should be a priority in ongoing trials.
Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. [2022]PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%), and pancreatitis (3%). Low-grade immune-related AEs were reported in 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune-related AEs occurred in 13% of the patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. The overall response rate (primary end point) was 67%, and the complete response (CR) rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% confidence interval, 8.2-27.6), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow-up of 35 months. The presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a CR and improved PFS. In this single-arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at www.clinicaltrials.gov as #NCT02446457.
Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. [2022]We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. Cancer Immunol Res; 6(3); 288-94. ©2018 AACR.
Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. [2022]Purpose: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer with programmed death ligand 1-positive (PD-L1-positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study.Patients and Methods: Patients with ER+/HER2- advanced breast cancer with PD-L1-positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review.Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3-15). Median follow-up was 9.7 months (range, 0.7-31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%-31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7-41). Median duration of response was 12.0 months (range, 7.4-15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred.Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1-positive, ER+/HER2- breast cancer. Clin Cancer Res; 24(12); 2804-11. ©2018 AACR.
FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. [2022]On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early-stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multicenter comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared with intravenous pertuzumab and intravenous trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of intravenous pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of intravenous trastuzumab. The primary endpoints were met with the observed lower limit of the two-sided 90% confidence intervals above the prespecified noninferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to intravenous, allowing for extrapolation and approval of all breast cancer indications for which intravenous trastuzumab and pertuzumab are approved.
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]The Chinese bridging study PUFFIN (NCT02896855) aimed to assess consistency of efficacy with CLEOPATRA (NCT00567190), investigating pertuzumab with trastuzumab and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer.
Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach. [2021]Pertuzumab plus trastuzumab, administered intravenously (IV) with chemotherapy, is standard treatment for HER2-positive metastatic or high-risk early breast cancer. Pertuzumab and trastuzumab are administered over 1-2.5 h traditionally; however, the need for IV infusions places a strain on medical centers with respect to scheduling, preparation, and administration. A novel fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PHESGO®, PH FDC SC) can be administered in approximately 5-8 min. PH FDC SC was non-inferior to IV pertuzumab plus trastuzumab in terms of pertuzumab and trastuzumab serum levels in the phase III FeDeriCa study, which enrolled 500 patients with HER2-positive early breast cancer. Total pathologic complete response rates were comparable after PH FDC SC (59.7%) or IV pertuzumab plus trastuzumab (59.5%), as was the incidence of grade ≥3 (48.8% vs 52.8%) and serious adverse events (16.1% vs 17.9%). The results of a phase II clinical trial (PHranceSCa) showed that a majority of patients (85%) preferred PH FDC SC treatment over IV pertuzumab plus trastuzumab. A US multicenter expanded access study (NCT04395508) is evaluating the safety of PH FDC SC administered at home by nurse providers in patients receiving maintenance HER2-targeted therapy every 3 weeks. This product takes much less time to administer than IV pertuzumab-trastuzumab and has the potential to alleviate time constraints for patients and busy clinics. In this review we provide an overview of PH FDC SC, and discuss our experience in preparing and administering this product to patients with HER2-positive breast cancer during clinical trials.