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

A Phase IB/II to Evaluate Efficacy and Safety of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: SHR6390; Drug: Letrozole or anastrozole or Fulvestrant

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Cancer Hospital, Chinese Academy of Medical Sciences
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China
      • Ha'erbin Tumor Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

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

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.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.

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

5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Part 1); Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).	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: Letrozole or anastrozole or Fulvestrant; Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or 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
Experimental: Cohort 2 (Part 1); SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).	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: Letrozole or anastrozole or Fulvestrant; Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or 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
Experimental: SHR6390 + Letrozole or anastrozole (Part 2); SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).	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: Letrozole or anastrozole or Fulvestrant; Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or 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
Experimental: SHR6390 + Fulvestrant Cohort 3 (Part 1); 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	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: Letrozole or anastrozole or Fulvestrant; Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or 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
Experimental: SHR6390 + Fulvestrant Cohort 4 (Part 1); 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	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: Letrozole or anastrozole or Fulvestrant; Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. Up to 24 months.	Up to 4 weeks

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.
Area under the plasma concentration versus time curve (AUC) of SHR6390		Up to 4 weeks
Peak Plasma Concentration (Cmax) of SHR6390		Up to 4 weeks
The time of SHR6390 to reach the maximum concentration (Tmax)		Up to 4 weeks
Half-time (t1/2) of SHR6390		Up to 4 weeks
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ¡Ý30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	Up to approximately 24 months.
Disease Control Rate (DCR) per RECIST 1.1	DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.	Up to approximately 24 months.
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.

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Binhe Xu, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): July 30, 2022
• Study Completion (Actual): July 30, 2022

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Breast cancer; HER2 negative; Postmenopausal women; CDK4/6 inhibitor; Premenopausal women; Hormone-receptor positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Letrozole; Fulvestrant; Anastrozole
• Other Study ID Numbers: SHR6390-Ib/II-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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