Clinical trial NCT05346328: HER2-positive Breast Cancer Project Initiated by Investigators
Official title: An Open-clinical Trial Phase Ⅱ, Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast Cancer；KL166-IIS-001
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HER2-positive Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-04-26
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study adopts an open research design and selects patients with refractory HER2-positive unresectable locally advanced or metastatic breast cancer who have failed previous ADC drug treatment. The patients who met the enrollment conditions were treated with injection of A166.
Primary purpose: TREATMENT

Brief summary: This study will assess the objective response rate (ORR), safety, progression-free survival (PFS) , overall survival (OS), 6-month survival rate, 12-month survival rate, 18-month survival rate, 24-month survival rate, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DOR) and Time to Response (TTR). Injection of A166 for HER2-positive patients with refractory unresectable locally advanced or metastatic breast cancer who have failed previous ADC drug therapy.


Eligibility criteria: Inclusion Criteria:

* 1. Male or female patient ≥ 18 years and ≤ 75 years when signing the informed consent form; 2. Breast cancer patients by histopathology and/or cytology documented, including:

  a) Participants with unresectable locally advanced or metastatic breast cancer; b) Evaluated or tested as HER2-positive expression. The definition of HER2 positive in this study: immunohistochemistry (IHC) was 2+ and confirmed by fluorescence in situ hybridization (FISH), or IHC was 3+; 3. Have received at least 3 targeted therapies for locally advanced or metastatic disease, including:
  1. Disease progression after receiving at least 1 trastuzumab-containing (including a biosimilar of trastuzumab on the market)-based treatment;
  2. After receiving at least one anti-HER2 tyrosine kinase inhibitor (lapatinib or pyrrotinib)-based treatment plan, the disease progresses or cannot tolerate toxic and side effects;
  3. The disease progresses or cannot tolerate toxic and side effects after receiving treatment with antibody-conjugated drugs targeting HER2 (such as T-DM1 or other ADCs); Note: Adjuvant therapy and anti-HER2 therapy used in the neoadjuvant treatment stage before radical treatment are not counted, but recurrence or metastasis occurs during the last anti-HER2 medication period or within one year after the end, it can be regarded as a plan.

     4. Have previously received taxanes to treat breast cancer;

     Exclusion Criteria:
* 1. Serious or uncontrollable heart diseases that require treatment, including:

  1. Congestive heart failure graded 3 or 4 by the New York College of Cardiology (NYHA);
  2. Unstable angina pectoris that cannot be controlled by drugs;
  3. Myocardial infarction occurred within 6 months before the first administration of the study treatment;
  4. Severe arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia); 2. Baseline measurement, QTc interval, male\> 450 msec, female\> 470 msec; 3. Clinically active interstitial lung disease; 4. Patients with primary central nervous system (CNS) malignant tumors or CNS metastases that have failed local treatment; for asymptomatic brain metastases, or with stable clinical symptoms and no need for steroids and other brain metastases within 4 weeks before the first administration of the trial drug Treated patients can be included in the group; 5. Those who are known to have a history of hypersensitivity to other monoclonal antibodies or allergic to A166 and its components for injection; 6. Those who have permanently discontinued trastuzumab due to any toxicity;

Primary outcomes:
measure: Objective response rate（ORR）
timeFrame: 2 years
Secondary outcomes:
measure: Progression-free survival(PFS)
timeFrame: 2 years
measure: Disease control rate(DCR)
timeFrame: 2 years
measure: Clinical benefit rate(CBR)
timeFrame: 2 years
measure: Duration of rate(DOR)
timeFrame: 2 years
measure: Time to response(TTR)
timeFrame: 2 years
measure: Overall survival(OS)
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Chief Physician
name: Xichun Hu, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. doi: 10.1016/S1470-2045(14)70178-0. Epub 2014 May 2.
citation: Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. doi: 10.1016/S1470-2045(17)30313-3. Epub 2017 May 16.