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

A Phase III Study to Evaluate the Efficacy and Safety of SHR6390 in Combination With Fulvestrant Versus Placebo Combined With Fulvesrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

This is a phase III clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Fulvestrant versus placebo combined with Fulvesrant in Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have received prior endocrine therapy are eligible for study.

Study Overview

• Status: Unknown
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: SHR6390; Drug: Fulvestrant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 357
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Chinese Academy of Medical Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 or prepostmenopausal women
3. Received prior endocrine therapy
4. One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.
5. Eastern Cooperative Oncology Group [ECOG] 0-1

Exclusion Criteria:

1. Patients who received prior treatment with any CDK4/6 inhibitor, everolimus or fulvestant.
2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR6390 + Fulvestrant; Intervention Drug: SHR6390, Fulvestrant	Drug: SHR6390; SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment; Drug: Fulvestrant; Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease
Placebo Comparator: Placebo + Fulvestrant; Intervention Drug: Placebo, Fulvestrant	Drug: Fulvestrant; Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease; Drug: Placebo; Placebo 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed PFS	Investigator-assessed Progression Free Survival	Up to approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per RECIST 1.1	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first.	Up to approximately 24 months.
OS	Overall Survival	Up to approximately 2 years
ORR	Objective Response Rate	Up to approximately 24 months.
DoR	Duration of Objective Response	Up to approximately 24 months
CBR	Clinical Benefit rate	Up to approximately 24 months.
AEs and SAEs	Number of Participants With adverse events (AEs) and serious adverse events (SAEs) Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.	Up to approximately 24 months.
Ctrough	Ctrough	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Liu YP, Hu MH, Lin PP, Li T, Liu SQ, Wang YY, Li SR, Li XK, Wang CJ, Cao Y. Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers. Drugs R D. 2022 Jun;22(2):175-182. doi: 10.1007/s40268-022-00390-7. Epub 2022 May 30.
• Xu B, Zhang Q, Zhang P, Hu X, Li W, Tong Z, Sun T, Teng Y, Wu X, Ouyang Q, Yan X, Cheng J, Liu Q, Feng J, Wang X, Yin Y, Shi Y, Pan Y, Wang Y, Xie W, Yan M, Liu Y, Yan P, Wu F, Zhu X, Zou J; DAWNA-1 Study Consortium. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021 Nov;27(11):1904-1909. doi: 10.1038/s41591-021-01562-9. Epub 2021 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2019
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 31, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: SHR6390-III-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No