Optimal Application Timing of ADC Drugs for Advanced Breast Cancer

NCT07657130 | Recruiting Phase 2

• 1 other identifier: OPTIMA-BC
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to initiate a prospective, randomized controlled trial to investigate the optimal timing of antibody drug conjugate (ADC) therapy in the management of advanced Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. Primary Objective: To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative breast cancer. Secondary Objectives: To compare overall survival (OS), adverse events, patient-reported outcomes, and cost-effectiveness between the two treatment sequences. Additionally, to identify potential biomarkers predictive of benefit from frontline ADC therapy.

Conditions

Breast Cancer Females

Keywords

Breast cancer; Antibody drug conjugate; Timing of application; Randomized controlled trial; HER2-negative

Outcome Measures

Primary Outcomes (1)

• Progression-free survival 2 (PFS2)

  Progression-free survival 2 (PFS2) is defined as the time from randomization to disease progression or death (whichever occurs first) following the second treatment.

  Up to approximately 20 months

Secondary Outcomes (4)

• Overall Survival (OS)

  Up to approximately 40 months

• Patient-Reported Outcomes (PROs)

  Up to approximately 20 months

• Time to Progression (TTP)

  Up to approximately 20 months

• Adverse event

  Up to approximately 20 months

Other Outcomes (2)

• Cost-effectiveness

  Up to approximately 20 months

• Exploratory Endpoint

  Up to approximately 20 months

Study Arms (2)

ADC followed by chemotherapy group

EXPERIMENTAL

Patients will receive an ADC agent as second-line treatment until disease progression or unacceptable toxicity, followed by physician's choice of chemotherapy as third-line treatment

Drug: Antibody drug conjugate; Drug: Chemotherapy

Chemotherapy followed by ADC group

ACTIVE COMPARATOR

Patients will receive physician's choice of chemotherapy as second-line treatment until disease progression or unacceptable toxicity, followed by an ADC agent as third-line treatment.

Drug: Antibody drug conjugate; Drug: Chemotherapy

Interventions

Antibody drug conjugate DRUG

The selection of ADC agents will be based on the patient's molecular subtype. For Hormone receptor (HR)+/HER2-low patients, anti-HER2 ADCs such as trastuzumab deruxtecan may be used. For HR+/HER2-zero patients, TROP-2-targeted ADCs such as sacituzumab govitecan are preferred. For HR-/HER2-low patients, either anti-HER2 ADCs or Trophoblast cell surface antigen 2 (TROP-2) ADCs may be considered. For HR-/HER2-zero patients, TROP-2 ADCs will be used. The specific ADC regimen will be determined at the discretion of the investigators.

ADC followed by chemotherapy group; Chemotherapy followed by ADC group

Chemotherapy DRUG

The chemotherapy regimen will consist of standard second-line agents such as capecitabine, eribulin, vinorelbine, or gemcitabine. The specific chemotherapy regimen will be determined at the discretion of the investigators.

ADC followed by chemotherapy group; Chemotherapy followed by ADC group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged 18-75 years;
• Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes;
• Completed first-line combination chemotherapy for advanced/metastatic disease (specific regimen not restricted), with disease progression (PD) evaluated per RECIST criteria (HR-positive patients must have received at least one line of endocrine therapy);
• Electrocorticography (ECOG) performance status \< 2;
• Estimated life expectancy ≥ 12 weeks;
• Adequate bone marrow function, defined as:
• ANC ≥ 1.5 × 10⁹/L
• Platelets ≥ 90 × 10⁹/L
• Hemoglobin ≥ 90 g/L
• Adequate hepatic and renal function, defined as:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• AST or ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases)
• Creatinine clearance ≥ 60 mL/min
• Signed informed consent obtained prior to any study-related procedures or treatments, confirming the patient's willingness to participate and comply with study requirements.

You may not qualify if:

• Prior treatment with an ADC after disease recurrence or metastasis;
• Pregnant or breastfeeding women;
• No evaluable recurrent or metastatic lesions as defined by RECIST 1.1 criteria;
• Symptomatic brain parenchymal and/or leptomeningeal metastases with symptoms not adequately controlled by treatment;
• History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, or well-controlled localized basal cell carcinoma of the skin;
• Psychiatric disorders or other conditions that may interfere with patient compliance;
• Recent history of serious and uncontrolled systemic diseases, such as clinically significant cardiovascular disease, pulmonary disease, metabolic disorders, or arterial/venous thromboembolic events;
• Concurrent use of other investigational drugs, or participation in another clinical trial within 30 days prior to enrollment;
• Known or suspected allergy to any study drug or its excipients;
• Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in this trial.

Sponsors & Collaborators

• Liaoning Cancer Hospital & Institute: lead
• National Cancer Center, China: collaborator

Study Sites (1)

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Immunoconjugates; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics

Study Officials

• Tao Sun

  Liaoning Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Bo Lan

  National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dan Lyu

CONTACT

0086-19800367870; lvdan9303@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: June 18, 2026
• Study Start: July 1, 2025
• Primary Completion: June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 18, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)