NCT06172127

PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer

A Multicenter, Open-Label, Single-Arm, Phase II Trial Exploring the Maintenance of Trastuzumab and Pertuzumab Following Trastuzumab Deruxtecan as Induction Treatment for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 165 (estimated)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

DEMETHER is an international, multicenter, open-label, single arm phase II clinical trial designed to evaluate the efficacy of a 6-cycle induction phase with T-DXd treatment followed by a maintenance phase with PHESGO treatment in patients with HER2-positive unresectable locally recurrent or MBC. Upon meeting all selection criteria, a total of 165 participants will be enrolled. Participants with no prior chemotherapy or HER2-targeted therapy for advanced or MBC (one prior line of endocrine therapy is allowed for MBC) will be eligible. Participants who have received neoadjuvant or adjuvant chemotherapy will be eligible, with a DFI from completion of systemic chemotherapy to advanced or metastatic diagnosis of \> 12 months. Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, discontinuation from the study treatment for any other reason, or up to 3 years (36 months) after T-DXd initiation, whichever occurs first. After discontinuation, all participants will undergo a safety visit at 28 (± 7 days) days after last treatment dose in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first. The main objectives of DEMETHER study are to determine the efficacy of induction treatment with T-DXd followed by PHESGO as maintenance therapy in terms of progression-free survival (PFS) rate at 1 year and overall survival (OS) rate at 3 years. End of study (EoS) is defined as the last data collection point at the last participant's safety visit and occur 36 months + 28 days (± 7 days) after the last patient included in the study initiates T-DXd treatment, unless premature termination of the study.

Conditions

• HER2-positive Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab deruxtecan	10 mL type 1 amber borosilicate glass vial sealed with a fluoro-resin laminated butyl rubber stopper, and a polypropylene/aluminium yellow flip-off crimp cap. One vial of powder for concentrate for solution for IV infusion contains 100 mg of T-DXd. The drug product also contains L-histidine, L-histidine hydrochloride monohydrate, Sucrose, and Polysorbate 80.
DRUG	Phesgo 1,200 MG / 600 MG / 30,000 UNT Per 15 ML Injection	20 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 15 mL solution of 1200 mg of pertuzumab and 600 mg of trastuzumab.
DRUG	Phesgo 600 MG / 600 MG / 20,000 UNT in 10 mL Injection	15 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 10 mL solution of 600 mg of pertuzumab and 600 mg of trastuzumab.

Timeline

• Start date: 2024-07-22
• Primary completion: 2026-11-01
• Completion: 2029-05-01
• First posted: 2023-12-15
• Last updated: 2025-07-29

Locations

36 sites across 5 countries: United States, France, Germany, Italy, Spain

Regulatory

• FDA-regulated drug study