A Study of BEBT-209 in Combination With Chemotherapy for the Treatment of Advanced Triple-Negative Breast Cancer

NCT06685796 | Recruiting Phase 2

• 1 other identifier: GBMT-209B-P01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter, open-label, two-stage Phase II clinical study to evaluate the safety and efficacy of BEBT-209 capsule in combination with carboplatin and gemcitabine for the treatment of advanced triple-negative breast cancer (TNBC).

Conditions

Advanced Triple-Negative Breast Cancer

Keywords

BEBT-209; Safety; Efficacy; In Combination With Chemotherapy

Outcome Measures

Primary Outcomes (2)

• PFS

  Progression-free survival

  From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• AE

  Adverse event

  From the first administration of the study drug to 28 days after the last administration of the study drug

Secondary Outcomes (5)

• OS

  From date of administration until date of death from any cause,assessed up to 24 months.

• ORR

  During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.

• DCR

  During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.

• TTR

  During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.

• DOR

  During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.

Study Arms (3)

Cohort 1：Carboplatin and Gemcitabine

EXPERIMENTAL

Carboplatin injection, dosage:AUC 2 ×(creatinine clearance rate + 25), frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle. Gemcitabine hydrochloride for injection, dosage:1000mg/m², frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle.

Drug: Carboplatin injection; Drug: Gemcitabine hydrochloride for injection

Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)

EXPERIMENTAL

BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally once before dinner, and on days 2 and 9, take orally once before breakfast. Carboplatin injection, dosage: AUC 2 × ( creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle. Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.

Drug: BEBT-209 capsules; Drug: Carboplatin injection; Drug: Gemcitabine hydrochloride for injection

Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)

EXPERIMENTAL

BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally twice (before breakfast and before dinner), and on days 2 and 9, take orally once before breakfast. Carboplatin injection, dosage: AUC 2 × (creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle. Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.

Drug: BEBT-209 capsules; Drug: Carboplatin injection; Drug: Gemcitabine hydrochloride for injection

Interventions

BEBT-209 capsules DRUG

BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally once before dinner or twice (before breakfast and before dinner), and on days 2 and 9, take orally once before breakfast.

Also known as: KCBT-0191

Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine); Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)

Carboplatin injection DRUG

Carboplatin injection, dosage: AUC 2 × (creatinine clearance rate + 25), frequency and duration of administration: administered on days 1 and 8 or days 2 and 9 of each cycle, with a 21-day cycle.

Also known as: NSC 241240

Cohort 1：Carboplatin and Gemcitabine; Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine); Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)

Gemcitabine hydrochloride for injection DRUG

Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 1 and 8 or days 2 and 9 of each cycle, with a 21-day cycle.

Also known as: NSC 613327

Cohort 1：Carboplatin and Gemcitabine; Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine); Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥18 years old, female;
• The subject has fully understood and is willing to sign the Informed Consent Form (ICF);
• Confirmed diagnosis of HR-negative, HER2-negative locally recurrent or metastatic breast cancer by pathological biopsy;
• Estrogen and progesterone receptor immunohistochemical assessment of tumor tissue is negative (defined as \<1% nuclear staining), and HER2 is negative (i.e., no overexpression, including local immunohistochemical assessment \[0 or 1+\], or immunohistochemical assessment \[2+\] with negative in situ hybridization testing);
• The subject has previously received 1-2 lines of systemic treatment (if progression within 12 months after the last treatment of adjuvant/new adjuvant, it can be considered as one line of treatment);
• At least one measurable lesion in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) score of 0-1 , and no decline in physical performance in the past two weeks;
• Life expectancy of at least 12 weeks;
• Adequate organ and bone marrow function, defined as follows:
• Absolute neutrophil count (ANC) ≥ 1500/mm³ (1.5 × 10\^9/L);
• Platelets ≥ 100,000/mm³ (100 × 10\^9/L);
• Hemoglobin ≥ 9 g/dL (90 g/L);
• Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) both ≤ 2.5 × ULN, when liver metastasis is present, ALT or AST both ≤ 5.0 × Upper limit of normal value (ULN);
• Total bilirubin (TBIL) ≤ 1.5 × ULN, when liver metastasis is present, ≤ 3.0 × ULN;
• Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (based on the Cockcroft and Gault formula);

You may not qualify if:

• Previous treatment with gemcitabine;
• Previous treatment with carboplatin for locally recurrent unresectable or metastatic breast cancer is allowed if it was administered in the adjuvant or neoadjuvant setting more than 6 months before the first metastatic relapse;
• Concurrent central nervous system metastases or leptomeningeal disease requiring immediate radiotherapy or corticosteroid treatment; patients must discontinue steroid medication for at least 14 days before the first administration of the study drug. No stereotactic radiosurgery within 7 days or whole brain radiotherapy within 14 days before the first administration of the study drug;
• Previous receipt of hematopoietic stem cell or bone marrow transplantation;
• Within 7 days prior to study entry, the patient has received the following treatments:
• Medications known to be strong inhibitors/inducers of CYP3A4;
• Medications known to significantly prolong the QT interval or cause torsades de pointes (antiarrhythmic drugs such as quinidine, disopyramide, procainamide, sotalol, etc.);
• Within 14 days prior to study entry, the patient has received radiotherapy, or within 21 days prior to study entry, the patient has received other investigational drug treatment or cytotoxic chemotherapy;
• Known history of hypersensitivity or suspected allergic symptoms to any component of BEBT-209, carboplatin, or gemcitabine;
• In a resting state, the average corrected QT interval (QTc) obtained from 3 Electrocardiogram (ECG) examinations is \>480msec (corrected using the Fridericia method); history of long QT syndrome or confirmed family history of long QT syndrome; history of clinically significant ventricular arrhythmias, or current use of antiarrhythmic drugs or implantation of defibrillation devices for the treatment of ventricular arrhythmias;
• Uncontrolled electrolyte disturbances that may affect the action of QTc-prolonging drugs (such as hypocalcemia \<1.0mmol/L, hypokalemia \< lower limit of normal, hypomagnesemia \<0.5mmol/L), but re-screening is allowed after interventional treatment;
• History of myocardial infarction, severe/unstable angina, persistent arrhythmias ≥ Grade 2 according to NCI CTCAE version 5.0, any grade of atrial fibrillation, coronary/ peripheral artery bypass surgery, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism);
• Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastrectomy; known malabsorption syndrome or other conditions that may impair the absorption of BEBT-209;
• Clinically significant active infections, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related diseases. Active hepatitis B is defined as positive for hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg), and HBV-DNA greater than the upper limit of normal for the research center. Patients with quantitative HBV DNA greater than the upper limit of normal for the research center are allowed to receive antiviral treatment before screening to reduce the viral load to within the normal range, but must continue to receive antiviral treatment for hepatitis B during the trial; active hepatitis C is defined as HCV RNA above the detection limit;
• Diabetes with poor blood sugar control as judged by the investigator;

Sponsors & Collaborators

• BeBetter Med Inc: lead

Study Sites (2)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Interventions

Carboplatin; Gemcitabine; Injections

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Quchang Ouyang, Phd

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Qiang Liu, Phd

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kegang Jiang, Master

CONTACT

+86-18664786382; kjiang@bebettermed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is designed with a total of 3 cohorts, enrolling patients with advanced triple-negative breast cancer. Subjets are randomly assigned to each cohort in a 1:1:1 ratio. Each cohort initially enrolls no fewer than 8 subjects for safety assessment, with the assessment period being the first cycle of medication (21 days). If the overall safety assessment is tolerable, the enrollment will be expanded to 30-40 subjects. During the trial, if the subjets in any of the above cohorts are unable to tolerate the treatment or there is no clinical benefit, the enrollment for that cohort will be terminated promptly.

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 13, 2024
• Study Start: April 12, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 13, 2024

Record last verified: 2024-11

Locations

CN (2)