A Study of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer

Hengrui Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Advanced Breast Cancer

Treatments: Drug: Letrozole or anastrozole or Fulvestrant; Drug: SHR6390

Study type: Interventional

Funder types: Industry

Identifiers

NCT03481998

SHR6390-Ib/II-201

Details and patient eligibility

About

This is a phase IB/II clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Letrozole or Anastrozole or Fulvestrant. Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have not received systemic anticancer therapy are eligible for study.

Enrollment: 104 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer.

2. Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration.

   Inclusion Criteria

3. Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease.

Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy:

1. a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

   b)Progressed within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

   c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal.

2. One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.

3. Eastern Cooperative Oncology Group [ECOG] 0-1 Measurable disease as per Response Evaluation Criterion in Solid Tumors[RECIST] 1.1

4. Adequate organ and marrow function

Exclusion Criteria

1. Confirmed diagnosis of HER2 positive disease
2. Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
3. Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant.
4. Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention.
5. Has known active central nervous system metastases.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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104 participants in 5 patient groups

Cohort 1 (Part 1)

Experimental group

Description:

Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Treatment:

Drug: Letrozole or anastrozole or Fulvestrant

Drug: SHR6390

Cohort 2 (Part 1)

Experimental group

Description:

SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Treatment:

Drug: Letrozole or anastrozole or Fulvestrant

Drug: SHR6390

SHR6390 + Letrozole or anastrozole (Part 2)

Experimental group

Description:

SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Treatment:

Drug: Letrozole or anastrozole or Fulvestrant

Drug: SHR6390

SHR6390 + Fulvestrant Cohort 3 (Part 1)

Experimental group

Description:

SHR6390 (at protocol defined dose levels), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily

Treatment:

Drug: Letrozole or anastrozole or Fulvestrant

Drug: SHR6390

SHR6390 + Fulvestrant Cohort 4 (Part 1)

Experimental group

Description:

SHR6390 (TBD), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily

Treatment:

Drug: Letrozole or anastrozole or Fulvestrant

Drug: SHR6390