Rising ctDNA to Tailor Endocrine Therapy Switch in Patients With ER+/HER2- Metastatic Breast Cancer.

NCT07717450 | Not Yet Recruiting Phase 3 DMC FDA Drug FDA Device

• 2 other identifiers: UC-BCG-25202025-524213-84-00
• Study Type: interventional
• Target: 370
• Locations: 0 countries
• Sites: N/A

Brief Summary

Rationale: In patients with metastatic breast cancer, fragments of tumor DNA called "circulating tumor DNA" or "ctDNA" can be detected in the blood. When the level of ctDNA increases, it often means that treatment is no longer effective and that the disease is likely to progress. Previous studies have shown that quickly changing hormone therapy as soon as a specific genetic anomaly (ESR1 mutation) is detected in the blood can improve outcomes for breast cancer patients. This monitoring also allows for earlier action against cells that are resistant to treatment. However, this mutation is only present in about 4 out of 10 women, which limits the use of this method to only some patients. Unlike previous approaches that targeted only the ESR1 mutation, the TAILORswitch study will assess a change in treatment following an increase in ctDNA, even in the absence of mutation, and before any other signs of disease progression. This change will include a new oral hormone therapy (camizestrant) combined with a targeted treatment that has shown benefits in cases of resistance (abemaciclib). This approach aims to intervene earlier in order to prevent disease progression. In summary, TAILORswitch explores a new way to personalize treatment, using more sensitive blood monitoring tools to improve quality of life and patient outcomes. Objectives: The primary objective of this trial is to demonstrate the efficacy of switching to camizestrant-abemaciclib combination therapy in patients with hormone-dependent metastatic breast cancer (ER+ HER2-) receiving targeted therapy combined with hormone therapy as first-line treatment, in cases where ctDNA levels increase without other signs of disease progression (clinical or radiological). Secondary objectives include:

• The efficacy, safety, and tolerability of the treatment switch
• The safety and feasibility of reducing the number of imaging exams in patients undergoing ctDNA monitoring every 3 months (optional substudy). Trial Design: TAILORswitch is a multi-step phase 3 randomized trial. Step 1 involves recruiting 370 patients with advanced or metastatic hormone-dependent breast cancer who are receiving CDK4/6 inhibitor and aromatase inhibitor therapy as their first treatment. Optional: some patients included in Step 1 will be offered to participate in a sub-study to evaluate imaging follow-up de-escalation. These patients will be allocated in of the following groups:
• Group A: maintenance of standard imaging every 3 to 4 months.
• Group B: reduction to imaging once per year at most, with a return to the standard frequency in case of clinical, radiological, biological, or ctDNA-based signs of progression. Step 2 involves patients who are initially eligible and show an increase in ctDNA levels without radiological progression. These patients will be allocated to one of the following groups:
• Group experimental: switch to the combination of camizestrant + abemaciclib until progression.
• Group control: continuation of standard treatment (AI + CDK4/6i) until progression. The recruitment period is 30 months, with the aim of including 156 patients in Step 2. Each participant will be followed for 30 months after inclusion.

Conditions

Metastatic Invasive Breast Cancer

Keywords

ctDNA monitoring; ER+ HER2- advanced breast cancer; de-escalate serial tumor imaging; watch and switch; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival is defined as the time from randomization in step #2 until the date of objective disease progression per RECIST 1.1 as assessed by local investigator or death due to any cause, whichever occurs first.

  from the date of randomization in step#2 to the date of first event (progression or death), up to 5 years after the first inclusion in the study

Secondary Outcomes (9)

• Related to Step #1: assess the feasibility of imaging de-escalation

  from the date of randomization in the substudy to the date of first event (molecular progression; RECIST or death), assessed up to 5 years after the first inclusion in the study

• Related to Step #1: To assess the safety of imaging de-escalation

  from the date of randomization in the sub-study to the date of first event (molecular progression; RECIST or death), assessed up to 5 years after the first inclusion in the study

• Related to Step #2: Progression free survival by subgoups according to stratification factors

  from the date of randomization in step#2 to the date of first event (progression or death), up to 5 years after the first inclusion in the study

• Related to Step #2: Progression free survival 2

  from randomisation in step#2 to the earliest progression after the 1st progression, or death from any cause; up to 5 years after the first inclusion in the study

• Related to Step #2: Time to chemotherapy

  from randomisation in step#2 until the start date of the 1st subsequent chemotherapy treatment after discontinuation of randomised treatment; up to 5 years after the first inclusion in the study

Study Arms (2)

Arm C: Continuation of standard-of-care treatment

ACTIVE COMPARATOR

Participants will continue their treatment with the same AI and CDK4/6 inhibitor (ribociclib or palbociclib) they received previously in Step #1 until disease progression (per RECIST v1.1, locally assessed). Then, they will be treated per standard of care.

Procedure: Tumor assessment; Other: Completion of Quality-of-life questionnaires

Arm D: Switch from AI to camizestrant and from ribociclib/palbociclib to abemaciclib

EXPERIMENTAL

Participants will discontinue the treatment received during Step #1 and be switched to camizestrant 75 mg once daily and abemaciclib 150mg twice daily.

Procedure: Tumor assessment; Other: Completion of Quality-of-life questionnaires; Procedure: ECG; Procedure: Visual Acuity assessment

Interventions

Tumor assessment PROCEDURE

Tumor assessment by RECIST 1.1 performed every 2 months the first 6 months then every 3 months during the participant visit at the hospital.

Arm C: Continuation of standard-of-care treatment; Arm D: Switch from AI to camizestrant and from ribociclib/palbociclib to abemaciclib

ECG PROCEDURE

12-lead ECG if allocated to arm D

Arm D: Switch from AI to camizestrant and from ribociclib/palbociclib to abemaciclib

Visual Acuity assessment PROCEDURE

Visual acuity assessment if allocated to arm D and if indicated

Arm D: Switch from AI to camizestrant and from ribociclib/palbociclib to abemaciclib

Completion of Quality-of-life questionnaires OTHER

Completion of Quality-of-life questionnaires: EORTC QLQ-C30 and BR42

Arm C: Continuation of standard-of-care treatment; Arm D: Switch from AI to camizestrant and from ribociclib/palbociclib to abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Related to Step #1
• First written informed consent (ICF#1) prior to any trial specific procedures. When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant's consent;
• Men or women ≥ 18 years of age;
• Eastern Cooperative Oncology Group performance status of 0 or 1;
• ER+ HER2- advanced (metastatic or locally advanced inoperable) breast adenocarcinoma (ER-positivity threshold: ≥10% tumor cells; HER2-negative tumour is defined as an immunohistochemical (IHC) score of 0 or 1+, or an IHC score of 2+ with negative in situ hybridization (ISH) (HER2/CEP17 ratio \<2 or, for single probe assessment, HER2 copy number \<4, according to the most recent available results), not amenable to resection or radiation therapy with curative intent;
• Eligible to (per investigator assessment) or currently receiving for up to 3 years, AI (+/- LH-RH agonist) and CDK4/6i (palbociclib or ribociclib) as first line therapy with adequate cardiac, renal, hematological and hepatic functions per investigator assessment;
• Evaluable disease (RECIST v1.1) before the start of AI+CDK4/6i and, in participants currently receiving AI and CDK4/6i, no evidence of clinical or radiological progression since AI+CDK4/6i initiation;
• Must have an adequate archival tumor tissue sample available (with a cellularity \> 30%) for centralized WGS analysis to design the ctDNA test. Requirements:
• Pre/perimenopausal women and fertile men must agree to use adequate contraception methods during the study:
• Female participants must be using highly effective standard-of-care non-hormonal contraceptive measures from the time of screening until 3 weeks after exiting from Step #1 (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly); or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: (a) Post-menopausal, defined as women with: (i) Cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; (ii) Cessation of regular menses for at least 6 consecutive months with no alternative pathological or physiological cause AND with serum estradiol and follicle stimulating hormone level within the laboratory's reference range for post-menopausal females; (iii) Previous bilateral surgical oophorectomy.
• Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception until at least one week after the last treatment administration.
• Minimum life expectancy of at least 6 months;
• Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;
• Participants must be affiliated with a social security scheme or a beneficiary of such a scheme (or equivalent);
• Additional criteria to be part of the imaging de-escalation sub-study in Step #1:

You may not qualify if:

• Related to step #1:
• Systemic antineoplastic therapy (except adjuvant therapies) received prior to AI and CDK4/6i;
• Known leptomeningeal metastasis and/or brain metastasis;
• Known contraindication to camizestrant and abemaciclib, per investigator assessment;
• Prior exposure to camizestrant, other SERD or investigational endocrine therapy agents;
• History of another malignancy, except (i) those treated with curative intent and with no known active disease ≥3 years; (ii) adequately treated non-melanoma cutaneous and in-situ cervix cancer;
• History of bone marrow transplantation;
• Patients relapsing while on or during the year after the discontinuation of adjuvant CDK4/6 inhibitor.
• Pregnant women or women who are breast-feeding or participants not willing to apply highly effective contraception as defined in the protocol;
• Participants unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;
• Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to participant enrolment and for the duration of the study);
• Persons deprived of their liberty or under protective custody or guardianship;
• Related to step #2:
• Participants with synchronous disease progression per local assessment (tumor imaging performed within 28 days prior to entry in Step #2 RECIST v1.1);
• Participants with a contraindication to abemaciclib, as assessed by the investigator;

Sponsors & Collaborators

• UNICANCER: lead
• AstraZeneca: collaborator
• Natera, Inc.: collaborator
• Institut du Cancer de Montpellier - Val d'Aurelle: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• François-Clément BIDARD, Pr/MD

  Institut Curie (France)

  STUDY CHAIR

Central Study Contacts

Clara Guyonneau, PharmD

CONTACT

0685167111; c-guyonneau@unicancer.fr

François-Clément BIDARD, MD

CONTACT

+33 (0)1 44 32 40 00; francois-clement.bidard@curie.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: TAILORswitch is an international, multistep randomized trial following a phase 3 design for its primary objective (Step 2). In Step 1, 370 patients will undergo serial ctDNA monitoring (baseline then every 3 months) while receiving first-line standard of care: AI combined with a CDK4/6 inhibitor (ribociclib or palbociclib) for advanced ER+ HER2- breast cancer. Patients with rising ctDNA without disease progression may enter Step 2, where 156 patients will be randomized (open-label): * Arm C: continuation of initial AI + CDK4/6i * Arm D: switch to camizestrant + abemaciclib In Step#1 an optional sub-study will assess imaging de-escalation. Eligible Step 1 patients will be randomized: * Arm A: standard imaging (every 3-4 months) * Arm B: reduced imaging (max once/year), resumed if progression signs or rising ctDNA occur. Participants included in the sub-study may proceed to Step #2 if a rising ctDNA is detected.

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 25, 2026
• Primary Completion (Estimated): June 25, 2032
• Study Completion (Estimated): June 25, 2032
• Last Updated: July 21, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share