A Multicenter, Open Phase II Clinical Study on the Safety and Efficacy of BEBT-109 Combined With Chemotherapy as First-Line Treatment for Non-Small Cell Lung Cancer Carrying EGFR Exon 20 Insertion Mutations
Overview
- Phase
- Phase 2
- Intervention
- BEBT-109 Capsules
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- BeBetter Med Inc
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
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.
Detailed Description
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 BEBT-109 monotherapy (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). Dose group A will first enroll six subjects to receive one cycle (a treatment cycle is 21 days) of drug treatment, and the safety data of subjects in dose group A will determine whether to adjust the dose for cohort 1 or to initiate other dose groups. If ≤2 subjects experience dose-limiting toxicity (DLT) during the DLT observation period, dose group A will be expanded to 20-30 subjects, and the decision to initiate dose group B will be made jointly by the investigators and the sponsor. If more than 2 subjects experience DLT, the decision to continue the study or to initiate dose group C will be made jointly by the investigators and the sponsor. Subjects in dose groups B and C will also initially enroll six subjects to undergo DLT safety follow-up, and then the decision to expand to 20-30 subjects will be made jointly by the investigators and the sponsor. The decision to initiate cohort 2 will be based on the safety and efficacy results from cohort 1. Each subject's study process includes three phases: screening, treatment, and follow-up. During the treatment period, subjects will undergo tumor assessments every 6 weeks ± 7 days. After discontinuing treatment, subjects will enter the follow-up period, where subjects without progressive disease (PD) will receive efficacy follow-up every 6 weeks ± 7 days (until tumor progression, death, or other antitumor treatment is initiated), and survival follow-up every 3 months (± 2 weeks). All subjects will receive study drug treatment until PD, death, intolerable toxicity occurs, or the subject withdraws informed consent (whichever occurs first).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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);
Exclusion Criteria
- •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;
Arms & Interventions
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: BEBT-109 Capsules
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Pemetrexed Disodium for Injection
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Carboplatin Injection
Dose group A of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Cisplatin Injection
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: BEBT-109 Capsules
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Pemetrexed Disodium for Injection
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Carboplatin Injection
Dose group B of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Cisplatin Injection
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: BEBT-109 Capsules
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Pemetrexed Disodium for Injection
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Carboplatin Injection
Dose group C of BEBT-109 combined with investigator-selected chemotherapy
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.
Intervention: Cisplatin Injection
BEBT-109 monotherapy
BEBT-109 Capsules: Administration and Dosage: Oral administration, 180mg; Frequency and Duration of Administration: Once a day,and 21 days as a treatment cycle.
Intervention: BEBT-109 Capsules
Outcomes
Primary Outcomes
ORR
Time Frame: Every 6 weeks,assessed up to 24 months.
Objective response rate
AE
Time Frame: From the first administration of the study drug to 28 days after the last administration of the study drug.
Adverse event
Secondary Outcomes
- DCR(Every 6 weeks,assessed up to 24 months.)