A Phase Ib Study of GB491 Plus Letrozole in Patients With Advanced Breast Cancer

Advanced Breast Cancer Clinical Trial

Official title:

A Multicenter, Open-label, Phase Ib Clinical Trial of GB491 in Combination With Letrozole in Previously Untreated Patients With HR-positive, HER2-negative Advanced Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05337657
• Other study ID #: GB491-005
• Status: Recruiting
• Phase: Phase 1
• Start date: June 2, 2021
• Est. completion date: February 1, 2024

Study information

• Verified date: December 2021
• Source: Genor Biopharma Co., Ltd.
• Contact: Shawn Yu
• Phone: 021-60751991
• Email: shawn.yu[@]genorbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GB491-005 is a multicenter, open-label, phase Ib Clinical Trial study to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of GB491 in combination with Letrozole in Previously Untreated Patients with HR-positive, HER2-negative Advanced Breast Cancer

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: February 1, 2024
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Females of 18 years of age or older at study screening

2. Histologically or cytologically confirmed locally advanced or advanced metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy

3. The subject has been diagnosed with ER-positive breast cancer in the local laboratory

4. The subject has HER2-negative breast cancer in the local laboratory

5. Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state)

6. No previous systemic anti-tumor treatment for locally advanced or metastatic breast cancer;

7. According to RECIST V1.1, the patient has at least one measurable lesion that has not been irradiated by radiotherapy and can be evaluated by CT/MRI; If only bone metastases are present, there must be at least one osteolytic bone lesion that can be evaluated by CT/MRI

8. ECOG performance status of 0 or 1

9. Adequate organ and marrow function.

10. The subject of childbearing potential must use one highly effective birth control method from the total duration of the study and 6 months after the last dose of study intervention.

11. Provide informed consent

Exclusion Criteria:

1. Previous treatment with CDK4/6 inhibitors

2. Subjects with known hypersensitivity to any component of GB491 or Letrozole

3. Patients with disease progression or recurrence during or within 1 year after completion of previous endocrine neoadjuvant or adjuvant therapy

4. Known active, uncontrolled, or symptomatic central nervous system metastasis, carcinomatous meningitis, or clinically manifested leptomeningeal disease, cerebral edema, spinal compression or/and tumor progressive growth

5. Visceral crisis

6. Patients with skin lesion only and radiographically non-measurable at baseline

7. Persistent toxicities (CTCAE Grade = 2) caused by previous anticancer therapy, excluding alopecia

8. Major surgical procedure within 4 weeks of the first dose of study treatment or an anticipated need for major surgery, chemotherapy, radiotherapy, any other investigational drug or other anti-cancer therapy during the study

9. Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 14 days prior to randomization

10. Patients who have received limited field radiotherapy in 2 weeks or extended field radiotherapy in 4 weeks before randomization or radiation with more than 30% of the bone marrow

11. Subjects use drugs or fruits containing strong inducers or inhibitors of CYP3A4/5, or drugs with narrow therapeutic window that are mainly metabolized by CYP3A4/5 in 14 days before randomization

12. Patients with long-term systematic use of corticosteroids

13. Any severe and/or uncontrollable medical conditions

14. Patients with severely impaired lung function

15. Known history of HIV infection or history of HIV seropositivity

16. Resting QTcF > 480 msec or there is a medical history of QTcF prolongation

17. Subjects have significant hepatic disease

18. Coagulation abnormalities

19. Refractory nausea and vomiting, inability to swallow the formulated product, or other disease or clinical status would preclude adequate absorption, distribution, metabolism, or excretion of GB491

20. Previous allogeneic bone marrow transplant

21. Inflammatory breast cancer;

22. Subjects with a history of other primary malignancies, except for non-melanoma skin cancer and cervical cancer in situ disease-free status = 3 years

23. Lactating women

24. Unlikely to comply with study procedures, restrictions, and requirements

25. Judgment by the investigator that the patient should not participate into the study

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• GB491+Letrozole
Drug:The dose of GB491 is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Genor Biopharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	Number of Participants with Dose-Limiting Toxicities for GB491 in Combination with Letrozole	During Cycle 1 (up to 28 days)
Primary	AE	Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)	From Baseline until 30 days after the last treatment
Secondary	PFS	To assess the progression free survival assessed by investigator	Approximately 2 years
Secondary	ORR	To assess the objective response rate for GB491 in Combination with Letrozole	Approximately 2 years
Secondary	DOR	To assess the duration of response for GB491 in Combination with Letrozole	Approximately 2 years
Secondary	DCR	To assess the disease control rate for GB491 in Combination with Letrozole	Approximately 2 years
Secondary	CBR	To assess the clinical benefit rate for GB491 in Combination with Letrozole by investigator	Approximately 2 years
Secondary	Plasma Concentration of GB491	Plasma Concentration of GB491 Over Time	At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days)
Secondary	Plasma Concentration of Letrozole	Plasma Concentration of Letrozole Over Time	At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days)