Immune Therapy in HR-positive/HER2-negative Metastatic Breast Cancer(ENIGMA)-BCTOP-L-M02

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Cancer; Breast Cancer

Treatments: Drug: AI; Drug: SERD; Drug: Nab paclitaxel; Drug: SHR6390; Drug: SHR-1316

Study type: Interventional

Funder types: Other

Identifiers

NCT05205200

FUSCC

Details and patient eligibility

About

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

Full 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.

Enrollment: 338 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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338 participants in 5 patient groups

Cohort 1A

Experimental group

Description:

In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1316 (anti-PD-L1) and endocrine therapy.

Treatment:

Drug: SERD

Drug: SHR6390

Drug: SHR-1316

Drug: AI

Cohort 1B

Active Comparator group

Description:

In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with endocrine therapy.

Treatment:

Drug: SERD

Drug: SHR6390

Drug: AI

Cohort 2A

Experimental group

Description:

In this cohort, a patient would receive SHR1316 (anti-PD-L1) combined with nab-paclitaxel.

Treatment:

Drug: Nab paclitaxel

Drug: SHR-1316

Cohort 2B

Active Comparator group

Description:

In this cohort, a patient would single nab-paclitaxel.

Treatment:

Drug: Nab paclitaxel

Cohort 2C

Other group

Description:

In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with fulvestrant.

Treatment:

Drug: SERD

Drug: SHR-1316