Clinical trial NCT05205200: Immune Therapy in HR-positive/HER2-negative Metastatic Breast Cancer(ENIGMA)-BCTOP-L-M02
Official title: Immune Therapy in HR-positive/HER2-negative Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: first-line therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: First Hospital of China Medical University
name: Sun Yat-sen University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Liaoning Cancer Hospital & Institute
name: Chongqing University Cancer Hospital
name: Northern Jiangsu People's Hospital
name: Fujian Medical University Union Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Shanghai First Maternity and Infant Hospital
name: Shanghai 6th People's Hospital
name: Affiliated Hospital of Nantong University
First posted: 2022-01-25
Enrollment: 338
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, open-label, phase II clinical study for patients with HR+/HER2- advanced breast cancer.

Detailed description: Patients with SNF2 subtype of HR+/HER2- advanced breast cancer confirmed by the Department of Pathology and Key Laboratory of Breast Cancer of Fudan University Affiliated Cancer Hospital are planned to be enrolled. Five treatment arms were set up based on the whether they have exposed to CDK4/6 inhibitors before. The main purpose is to evaluate immune therapy in SNF2 subtype of HR+/HER2- advanced breast cancer and prepare for subsequent randomized controlled phase III clinical studies with larger sample size.

Eligibility criteria: Inclusion Criteria:

* Females ≥18 years and ≤ 75 years old;
* Histologically confirmed HR + / HER2- invasive breast cancer (specific definition: immunohistochemical detection of ER\> 10% tumor cell positive is defined as ER positive, PR\> 10% tumor cell positive is defined as PR positive, ER and / or PR Positive is defined as HR positive; HER2 0-1 + or HER2 is ++ but negative followed by FISH detection, no amplification, defined as HER2 negative);
* Subtype of similarity network fusion-2 (SNF-2) confirmed by the Department of Pathology and Key Laboratory of Breast Cancer of Fudan University Affiliated Cancer Hospital
* Locally advanced breast cancer (incapable of radical local treatment) or recurrent metastatic breast cancer;
* Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1); or unmeasurable lytic or mixed (osteolytic + osteoblastic) bone lesions in the absence of measurable lesions;
* Has adequate bone marrow function: absolute neutrophil count \> 1.5x10ˆ9 /L; platelet count \> 75x10ˆ9 /L, hemoglobin \> 9g/dL;
* Patients had received no previous chemotherapy or targeted therapy for metastatic disease
* Has adequate liver function and kidney function: serum creatinine
* ECOG score ≤ 2 and life expectancy ≥ 3 months;
* Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.

Exclusion Criteria:

* Treatment with chemotherapy, radiotherapy, immunotherapy or surgery (outpatient clinic surgery excluded) for metastatic disease

  * Symptomatic, untreated, or actively progressing CNS metastases(glucocorticoids or mannitol needed to control symptoms);
  * Significant cardiovascular disease(including congestive heart failure, angina pectoris, myocardial infarction or ventricular arrhythmia in the last 6 months);
  * is pregnant or breast feeding;
  * Malignant tumors in the past five years (except cured skin basal cell carcinoma and cervical carcinoma in situ).
  * History of autoimmune disease
  * Positive test for human immunodeficiency virus
  * Active hepatitis B or hepatitis C
  * Uncontrolled pleural effusion and ascites
  * Thyroid dysfunction.

Primary outcomes:
measure: PFS
timeFrame: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
Secondary outcomes:
measure: ORR
timeFrame: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
measure: CBR
timeFrame: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
measure: OS
timeFrame: Randomization to death from any cause, through the end of study (approximately 5 years)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai cancer center
Study officials:
affiliation: Fudan University
name: Zhi-Ming Shao
role: PRINCIPAL_INVESTIGATOR
References: