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

Primary Purpose

Breast Cancer, Metastatic Cancer

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

SHR-1316

SHR6390

Nab paclitaxel

SERD

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring first-line therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

Fudan University Shanghai cancer centerRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Other

Arm Label

Cohort 1A

Cohort 1B

Cohort 2A

Cohort 2B

Cohort 2C

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

PFS

time to progressive disease (according to RECIST1.1)

Secondary Outcome Measures

ORR

The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

CBR

the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the

time to death due to any cause

Full Information

NCT ID

NCT05205200

First Posted

January 11, 2022

Last Updated

May 7, 2023

Sponsor

Fudan University

Collaborators

Peking University Cancer Hospital & Institute, First Hospital of China Medical University, Sun Yat-sen University, First Affiliated Hospital Xi'an Jiaotong University, Liaoning Tumor Hospital & Institute, Chongqing University Cancer Hospital, Northern Jiangsu Province People's Hospital, Fujian Medical University Union Hospital, Ningbo Medical Center Lihuili Hospital, Shanghai First Maternity and Infant Hospital, Shanghai 6th People's Hospital, Affiliated Hospital of Nantong University

1. Study Identification

Unique Protocol Identification Number

NCT05205200

Brief Title

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

Official Title

Immune Therapy in HR-positive/HER2-negative Metastatic Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 6, 2022 (Actual)

Primary Completion Date

February 1, 2025 (Anticipated)

Study Completion Date

August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Metastatic Cancer

Keywords

first-line therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

338 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1A

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 1B

Arm Type

Active Comparator

Arm Description

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

Arm Title

Cohort 2A

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 2B

Arm Type

Active Comparator

Arm Description

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

Arm Title

Cohort 2C

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

SHR-1316

Intervention Description

PD-L1 antibody

Intervention Type

Drug

Intervention Name(s)

SHR6390

Intervention Description

CDK4/6 inhibitor

Intervention Type

Drug

Intervention Name(s)

Nab paclitaxel

Intervention Description

Albumin bound paclitaxel

Intervention Type

Drug

Intervention Name(s)

SERD

Intervention Description

Fulvestrant

Intervention Type

Drug

Intervention Name(s)

Intervention Description

aromatase inhibitor

Primary Outcome Measure Information:

Title

PFS

Description

time to progressive disease (according to RECIST1.1)

Time Frame

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 Outcome Measure Information:

Title

ORR

Description

The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Time Frame

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)

Title

CBR

Description

the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the

Time Frame

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)

Title

Description

time to death due to any cause

Time Frame

Randomization to death from any cause, through the end of study (approximately 5 years)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhi-Ming Shao

Phone

86-021-64175590

Ext

8888

zhimingshao@yahoo.com

First Name & Middle Initial & Last Name or Official Title & Degree

Zhong-Hua Wang

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhi-Ming Shao

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai cancer center

City

Shanghai

ZIP/Postal Code

200032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Min U He, M.D.

Phone

021-64175590

Ext

88603

minsmiler@126.com

12. IPD Sharing Statement

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

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