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OncoMatch/Clinical Trials/NCT07647016

Trastuzumab Deruxtecan Plus ivonescImab for Hormone Receptor-positive HER2 Negative Advanced Breast Cancer Study

Is NCT07647016 recruiting? Yes, currently enrolling (Jul 2026). This Phase 2 trial studies Trastuzumab Deruxtecan and ivonescimab for breast cancer.

Phase 2RecruitingFudan UniversityNCT07647016Data as of Jul 2026Location: China

Treatment: Trastuzumab Deruxtecan and ivonescimabThe UNITY study is a prospective, single-arm, single-center, Phase II clinical trial conducted by Fudan University Shanghai Cancer Center. It aims to evaluate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) combined with ivonescimab in patients with hormone receptor-positive (HR+), HER2-negative recurrent or metastatic breast cancer. Approximately 53 patients will be enrolled. Eligible participants must have histologically confirmed advanced HR-positive breast cancer with HER2-low or HER2-ultralow expression. They must have experienced recurrence, metastasis, or disease progression after prior treatment with a CDK4/6 inhibitor (including in the adjuvant setting) and have received at most one line of systemic chemotherapy for advanced disease. The study permits the enrollment of patients with central nervous system (CNS) metastases. The primary endpoint is the Overall Response Rate (ORR). Key secondary endpoints include Clinical Benefit Rate (CBR), Overall Survival (OS), Progression-Free Survival (PFS), safety, and patient-reported quality of life (assessed using EORTC QLQ-C30 and QLQ-BR23). Exploratory endpoints will involve the analysis of biomarkers from tumor and blood samples, as well as PAM50 molecular subtyping and its correlation with survival outcomes. This study seeks to explore the efficacy and safety of Trastuzumab Deruxtecan in combination with ivonescimab for patients with HR-positive, HER2-negative recurrent or metastatic breast cancer, with a particular focus on the subpopulation with CNS metastases.

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Extracted eligibility criteria

Treatments studied

Targeted therapy

Trastuzumab Deruxtecan and ivonescimab

Cancer type

Breast Carcinoma

Biomarker criteria

Required: ESR1 expression (≥1% positive cells)

HR positivity is defined as Estrogen Receptor (ER) positive (≥1% positive cells) and/or Progesterone Receptor (PR) positive (≥1% positive cells)

Required: PR (PGR) expression (≥1% positive cells)

HR positivity is defined as Estrogen Receptor (ER) positive (≥1% positive cells) and/or Progesterone Receptor (PR) positive (≥1% positive cells)

Required: HER2 (ERBB2) overexpression (HER2 (0 with staining), HER2 (1+), or HER2 (2+) by IHC with a negative ISH result)

HER2-low or HER2-ultralow expression is defined as HER2 (0 with staining), HER2 (1+), or HER2 (2+) by immunohistochemistry (IHC) with a negative in-situ hybridization (ISH) result

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Max 1 prior line

Must have received: CDK4/6 inhibitor — any (including adjuvant)

History of recurrence or disease progression after prior treatment with a CDK4/6 inhibitor (including in the adjuvant setting)

Cannot have received: anti-PD-1 therapy

Exception: Allowed if no progression during therapy AND ≥3 months between last dose and recurrence/progression

Prior treatment with anti-PD-1/PD-L1 or anti-VEGF agents, unless both of the following conditions are met: (1) The patient did not experience disease progression during treatment with the anti-PD-1/PD-L1 or anti-VEGF agent; and (2) The time from the last dose of the anti-PD-1/PD-L1 or anti-VEGF agent to the time of recurrence or disease progression is ≥ 3 months.

Cannot have received: anti-PD-L1 therapy

Exception: Allowed if no progression during therapy AND ≥3 months between last dose and recurrence/progression

Prior treatment with anti-PD-1/PD-L1 or anti-VEGF agents, unless both of the following conditions are met: (1) The patient did not experience disease progression during treatment with the anti-PD-1/PD-L1 or anti-VEGF agent; and (2) The time from the last dose of the anti-PD-1/PD-L1 or anti-VEGF agent to the time of recurrence or disease progression is ≥ 3 months.

Cannot have received: anti-VEGF therapy

Exception: Allowed if no progression during therapy AND ≥3 months between last dose and recurrence/progression

Prior treatment with anti-PD-1/PD-L1 or anti-VEGF agents, unless both of the following conditions are met: (1) The patient did not experience disease progression during treatment with the anti-PD-1/PD-L1 or anti-VEGF agent; and (2) The time from the last dose of the anti-PD-1/PD-L1 or anti-VEGF agent to the time of recurrence or disease progression is ≥ 3 months.

Cannot have received: trastuzumab deruxtecan (trastuzumab deruxtecan)

Prior treatment with trastuzumab deruxtecan or any antibody-drug conjugate (ADC) containing a topoisomerase inhibitor

Cannot have received: antibody-drug conjugate containing a topoisomerase inhibitor

Prior treatment with trastuzumab deruxtecan or any antibody-drug conjugate (ADC) containing a topoisomerase inhibitor

Lab requirements

Blood counts

ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L; Hemoglobin ≥ 90 g/L (transfusion or medical support permitted)

Kidney function

BUN or Serum Creatinine ≤ 1.5 × ULN, or Creatinine Clearance ≥ 50 mL/min (Cockcroft-Gault)

Liver function

Total Bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN (≤ 5.0 × ULN in the presence of liver metastases)

Cardiac function

QTcF < 470 ms for females and < 450 ms for males on ECG; LVEF ≥ 50% by echocardiogram

Adequate organ function, defined as follows: Hematology: ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L; Hemoglobin ≥ 90 g/L (transfusion or medical support to meet this level is permitted). Hepatic and Renal Function: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN (≤ 5.0 × ULN in the presence of liver metastases); BUN or Serum Creatinine ≤ 1.5 × ULN, or Creatinine Clearance ≥ 50 mL/min (Cockcroft-Gault). Coagulation: APTT ≤ 1.5 × ULN; PT ≤ 1.5 × ULN. Cardiac: QTcF < 470 ms for females and < 450 ms for males on ECG; LVEF ≥ 50% by echocardiogram.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

Frequently asked questions

Is NCT07647016 currently recruiting?

Yes, this trial is currently recruiting patients.

Are there prior therapy exclusions?

Yes. Prior anti-PD-1 therapy, anti-PD-L1 therapy, anti-VEGF therapy disqualifies patients from enrollment.

Does this trial require ESR1?

Yes, ESR1 expression is a required biomarker for enrollment.

Does this trial require PGR?

Yes, PGR expression is a required biomarker for enrollment.

Does this trial require ERBB2?

Yes, ERBB2 overexpression is a required biomarker for enrollment.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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