Study of BEBT-109 in Subjects With Non-Small Cell Lung Cancer Carrying EGFR Exon 20 Insertion Mutations

NCT06514027 | Not Yet Recruiting Phase 2

• 1 other identifier: GBMT-109-P04
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open Phase II clinical study to evaluate the efficacy, safety, and pharmacokinetic characteristics of BEBT-109 combined with injectable pemetrexed disodium and carboplatin or cisplatin injection as first-line treatment for locally advanced, recurrent, or metastatic non-small cell lung cancer carrying EGFR exon 20 insertion mutations.

Conditions

Non Small Cell Lung Cancer

Keywords

BEBT-109; EGFR exon 20 insertion mutations; Drug combination; First-line treatment; Safety; Efficacy

Outcome Measures

Primary Outcomes (2)

• ORR

  Objective response rate

  Every 6 weeks,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 (1)

• DCR

  Every 6 weeks,assessed up to 24 months.

Other Outcomes (9)

• DOR

  Every 6 weeks,assessed up to 24 months.

• PFS

  Every 6 weeks,assessed up to 24 months.

• OS

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

Study Arms (4)

Dose group A of BEBT-109 combined with investigator-selected chemotherapy

EXPERIMENTAL

BEBT-109 Capsules: Administration and Dosage: Oral administration, 180mg; Frequency and Duration of Administration: Once a day,and 21 days as a treatment cycle. Pemetrexed Disodium for Injection: Administration and Dosage: Intravenous infusion, 500mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle,and 21 days as a treatment cycle. Carboplatin Injection: Administration and Dosage: Intravenous infusion, AUC=5 mg/ml.min, with a single dose not exceeding 800 mg; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles. Cisplatin Injection: Administration and Dosage: Intravenous infusion, 75 mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles.

Drug: BEBT-109 Capsules; Drug: Pemetrexed Disodium for Injection; Drug: Carboplatin Injection; Drug: Cisplatin Injection

Dose group B of BEBT-109 combined with investigator-selected chemotherapy

EXPERIMENTAL

BEBT-109 Capsules: Administration and Dosage: Oral administration, 120mg; Frequency and Duration of Administration: Twice a day,and 21 days as a treatment cycle. Pemetrexed Disodium for Injection: Administration and Dosage: Intravenous infusion, 500mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle,and 21 days as a treatment cycle. Carboplatin Injection: Administration and Dosage: Intravenous infusion, AUC=5 mg/ml.min, with a single dose not exceeding 800 mg; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles. Cisplatin Injection: Administration and Dosage: Intravenous infusion, 75 mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles.

Drug: BEBT-109 Capsules; Drug: Pemetrexed Disodium for Injection; Drug: Carboplatin Injection; Drug: Cisplatin Injection

Dose group C of BEBT-109 combined with investigator-selected chemotherapy

EXPERIMENTAL

BEBT-109 Capsules: Administration and Dosage: Oral administration, 120mg; Frequency and Duration of Administration: Once a day,and 21 days as a treatment cycle. Pemetrexed Disodium for Injection: Administration and Dosage: Intravenous infusion, 500mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle,and 21 days as a treatment cycle. Carboplatin Injection: Administration and Dosage: Intravenous infusion, AUC=5 mg/ml.min, with a single dose not exceeding 800 mg; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles. Cisplatin Injection: Administration and Dosage: Intravenous infusion, 75 mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles.

Drug: BEBT-109 Capsules; Drug: Pemetrexed Disodium for Injection; Drug: Carboplatin Injection; Drug: Cisplatin Injection

BEBT-109 monotherapy

EXPERIMENTAL

BEBT-109 Capsules: Administration and Dosage: Oral administration, 180mg; Frequency and Duration of Administration: Once a day,and 21 days as a treatment cycle.

Drug: BEBT-109 Capsules

Interventions

BEBT-109 Capsules DRUG

BEBT-109 Capsules: Administration and Dosage: Oral administration, 120mg or 180mg; Frequency and Duration of Administration: Once a day or twice a day,and 21 days as a treatment cycle.

Also known as: KCBT-1083

BEBT-109 monotherapy; Dose group A of BEBT-109 combined with investigator-selected chemotherapy; Dose group B of BEBT-109 combined with investigator-selected chemotherapy; Dose group C of BEBT-109 combined with investigator-selected chemotherapy

Pemetrexed Disodium for Injection DRUG

Pemetrexed Disodium for Injection: Administration and Dosage: Intravenous infusion, 500mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle,and 21 days as a treatment cycle.

Dose group A of BEBT-109 combined with investigator-selected chemotherapy; Dose group B of BEBT-109 combined with investigator-selected chemotherapy; Dose group C of BEBT-109 combined with investigator-selected chemotherapy

Carboplatin Injection DRUG

Carboplatin Injection: Administration and Dosage: Intravenous infusion, AUC=5 mg/ml.min, with a single dose not exceeding 800 mg; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles.

Dose group A of BEBT-109 combined with investigator-selected chemotherapy; Dose group B of BEBT-109 combined with investigator-selected chemotherapy; Dose group C of BEBT-109 combined with investigator-selected chemotherapy

Cisplatin Injection DRUG

Cisplatin Injection: Administration and Dosage: Intravenous infusion, 75 mg/m\^2; Frequency and Duration of Administration: On the first day of each cycle for the first four cycles, and 21 days as a treatment cycle, totaling four cycles.

Dose group A of BEBT-109 combined with investigator-selected chemotherapy; Dose group B of BEBT-109 combined with investigator-selected chemotherapy; Dose group C of BEBT-109 combined with investigator-selected chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participants have a comprehensive understanding, voluntarily sign the Informed Consent Form (ICF), and are capable of completing all trial procedures;
• Age ≥18 years old, both males and females are eligible;
• According to the 8th edition of the American Joint Committee on Cancer（AJCC）TNM staging criteria for lung cancer: patients with histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) that is unresectable and intolerant or refuses radical synchronous radiochemotherapy, with locally advanced (stage IIIB or IIIC), recurrent, or metastatic (stage IV) disease;
• No prior systemic treatment for locally advanced (stage IIIB or IIIC) or recurrent/metastatic (stage IV) NSCLC. Note: 1) Neoadjuvant/adjuvant therapy is allowed as long as it has been completed at least 6 months before the disease is diagnosed as locally progressive or metastatic tumor; 2) Participants who have failed treatment with savolitinib in the past are allowed;
• EGFR exon 20 insertion mutations confirmed by peripheral blood or tumor tissue testing conducted by a tertiary hospital or a qualified third-party testing agency, and records must be provided. Patients may have only EGFR exon 20 insertion mutations or may also have other EGFR or HER2 mutations;
• At least one measurable lesion that meets the RECIST V1.1 criteria during the screening period. Lesions previously treated with radiotherapy cannot be used as target lesions unless there is clear radiological progression after radiotherapy;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, and no decline in performance status within two weeks before the screening period, with an expected survival time ≥12 weeks;
• Provided that the subject has not received blood transfusion, erythropoietin, recombinant human thrombopoietin, or colony-stimulating factor treatment within 14 days before the screening period, laboratory tests indicate that the subject has adequate organ function, including:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥100×10\^9/L; Hemoglobin (HGB) ≥90 g/L;
• Total serum bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) (for patients with Gilbert's syndrome, total bilirubin ≤3×ULN is allowed);
• AST and ALT ≤2.5×ULN (for those with liver metastasis, AST and ALT ≤5×ULN is allowed);
• Creatinine clearance ≥45 ml/min (calculated according to the Cockcroft-Gault formula), and urine protein ≤1+ or for subjects with urine protein ≥2+, the 24-hour urine protein total is ≤1 g/24 h;
• Activated partial thromboplastin time (APTT) ≤1.5×ULN, prothrombin time (PT) ≤1.5×ULN, international normalized ratio (INR) ≤1.5×ULN;
• Participants with a history of liver cirrhosis have a Child-Pugh score of A or B ≤7 at screening;
• The QT interval evaluated by ECG at screening is normal, defined as the corrected QT interval (Fridericia) (QTcF) ≤450 ms (for males) or ≤470 ms (for females) (those not meeting the standard need to be retested twice, and the average corrected value of the three measurements is taken);

You may not qualify if:

• History of severe allergic diseases (such as uncontrollable asthma), severe drug (including investigational drugs not yet marketed) allergies, or known allergies or intolerance to any drug or drug component in this study;
• Diagnosis of other primary malignant tumors besides NSCLC, except for the following: non-melanoma skin cancer or cervical carcinoma in situ that has been adequately treated and cured, non-metastatic prostate cancer, or other primary malignant tumors that have been clearly recurrence-free for at least 3 years since the last treatment and have a low potential risk of recurrence;
• Major surgical procedures within 28 days before the first administration of the study drug, planned surgery during the study period, or postoperative complications from surgery performed within 2 months before the first administration of the study drug (except for minor surgeries that the investigator deems do not affect participation in the trial, such as catheter placement or minimally invasive biopsy);
• Presence of pleural effusion, ascites, or pericardial effusion with significant symptoms or requiring drainage;
• Poorly controlled diabetes mellitus. Definition: Hemoglobin A1C (HbA1c) ≥8%; or 7% ≤ Hemoglobin A1C \< 8%, accompanied by clinical symptoms of diabetes, such as polyuria, polydipsia, polyphagia, and weight loss. (Subjects who have not been adequately treated to control blood sugar, after adjusting the drug treatment plan, with fasting blood glucose ≤10 mmol/L, and deemed suitable to participate in this study by the investigator, can be included);
• Received live vaccines within 28 days before the first administration of the study drug or plan to receive any live vaccines during the study period;
• Subjects with a tendency to bleed or evidence of bleeding, including:
• History of active ulcers or perforations of the stomach and duodenum within 6 months before the first dose, persistent positive fecal occult blood, history of gastrointestinal bleeding such as ulcerative colitis;
• History of hemoptysis (defined as blood that is bright red or 2.5 ml) within 2 weeks before the first dose, or the presence of unhealed wounds, ulcers, or fractures;
• Vasculitis;
• Other conditions that may cause bleeding as determined by the investigator;
• Presence of severe gastrointestinal functional abnormalities that may affect the intake, transport, or absorption of the test drug (such as inability to swallow, uncontrollable vomiting, history of extensive gastrointestinal resection, chronic diarrhea, long-term use of proton pump inhibitors (PPIs) for gastric diseases, Crohn's disease, ulcerative colitis, intestinal obstruction, etc.);
• Presence of central nervous system (CNS) metastasis, except for those who are asymptomatic, have stable disease, and do not require drug treatment within 4 weeks before the start of the study treatment;
• Current spinal cord compression (symptomatic or asymptomatic, and detected by radiographic examination) or suspected meningeal disease (symptomatic or asymptomatic);
• Imaging (CT or MRI) shows that the tumor invades major blood vessels or is not clearly demarcated from major blood vessels;

Sponsors & Collaborators

• BeBetter Med Inc: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Injections; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Drug Administration Routes; Drug Therapy; Therapeutics; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Li Zhang, Master

  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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study initially sets up two cohorts. In cohort 1, the treatment is BEBT-109 combined with investigator-selected chemotherapy (injectable pemetrexed disodium combined with carboplatin or cisplatin injection). In cohort 2, the treatment is monotherapy with BEBT-109 (BEBT-109 capsule at a dose of 180mg, taken orally once daily). Based on different dosing regimens of BEBT-109 capsules, cohort 1 is divided into three dose groups: A (BEBT-109 capsule at a dose of 180mg, taken orally once daily), B (BEBT-109 capsule at a dose of 120mg, taken orally twice daily), and C (BEBT-109 capsule at a dose of 120mg, taken orally once daily). The decision to initiate cohort 2 will be based on the safety and efficacy results from cohort 1.

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 23, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

CN (1)