Sequential Chemotherapy With Befotertinib in Non-Small Cell Lung Cancer (NSCLC) Patients With Resistance to Third-Generation EGFR-TKI

NCT ID: NCT07181499

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2028-12-31

Brief Summary

Non-small cell lung cancer (NSCLC) accounts for over 85% of lung cancers. Approximately 30-40% of East Asian adenocarcinoma patients harbor EGFR mutations. Third-generation EGFR-TKIs achieve a median PFS of about 20 months as first-line therapy, but resistance eventually develops. Studies like MARIPOSA-2 confirm that amivantamab combined with chemotherapy ± lazertinib or immunotherapy regimens (ivucitinib/sintilimab + bevacizumab + chemotherapy) can extend median PFS post-resistance from approximately 4 months to 6-8 months. As a third-generation TKI, befitinib has demonstrated PFS of 16-22 months in both first-line and post-T790M mutation settings. This study aims to further evaluate the feasibility and safety of "pemetrexed + carboplatin followed by befotertinib" for patients resistant to third-generation TKIs.

Conditions

NSCLC; Adjuvant Drug Therapy; EGFR

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

pemetrexed (500 mg/m2) and carboplatin (AUC 5), administered every 3 weeks. After 2 to 4 cycles, received Befotertinib (75-100 mg)

Group Type: EXPERIMENTAL

Befotertinib

Intervention Type: DRUG

Befotertinib was administered orally at a starting dose of 75 mg per day for 21 days, which could be increased to 100 mg per day if grade 2 or higher thrombocytopenia or headache did not occur within 21 days, or maintained at the original dose (75 mg per day) if grade 2 or higher thrombocytopenia or headache occurred within 21 days.

Pemetrexed + Carboplatin

Intervention Type: DRUG

pemetrexed (500 mg/m²) and carboplatin (AUC 5), administered every 3 weeks, for a total of 2\~4 cycles.

Interventions

Befotertinib

Befotertinib was administered orally at a starting dose of 75 mg per day for 21 days, which could be increased to 100 mg per day if grade 2 or higher thrombocytopenia or headache did not occur within 21 days, or maintained at the original dose (75 mg per day) if grade 2 or higher thrombocytopenia or headache occurred within 21 days.

Intervention Type: DRUG

Pemetrexed + Carboplatin

pemetrexed (500 mg/m²) and carboplatin (AUC 5), administered every 3 weeks, for a total of 2\~4 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years;

2. Histologically or cytologically confirmed advanced or metastatic non-squamous NSCLC; and prior resistance to third-generation EGFR TKIs, with EGFR-sensitive mutations confirmed via tissue or blood samples (defined as: 19 Del or 21 L858R);

3. Exclusion of small cell lung cancer (SCLC) or squamous cell carcinoma (SqCC) transformation, and known NSCLC with clear targetable mutations for targeted therapy, such as HER2, MET amplification (GCN ≥ 5), KRAS G12C mutation, BRAF V600E mutation, RET fusion mutation, ALK fusion mutation, NTRK fusion mutation, etc.;

4. ECOG performance status (PS) score of 0-2;

5. Life expectancy of at least 12 weeks;

6. Ability to swallow oral medications;

7. Adequate organ system function, defined as follows and determined based on investigator judgment:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L

2. Platelets ≥ 100 x 10⁹/L;

3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). Note: Blood transfusions are permitted to achieve the required hemoglobin level;

4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);

5. If no liver metastases: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if liver metastases present: ≤ 5 × ULN;

6. Creatinine ≤1.5 × ULN. If ≥1.5 × ULN, patients remain eligible if the Cockcroft-Gault-calculated creatinine clearance ≥50 mL/min (0.83 mL/s);

8. Female subjects of childbearing potential must have a negative serum pregnancy test within 3 days prior to study drug initiation and agree to use a medically approved highly effective contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 3 months after the last study drug administration; Male subjects with female partners of childbearing potential must be surgically sterilized or agree to use an effective method of contraception during the study period and for 3 months after the last study dose.

9. Voluntarily agree and be capable of adhering to the trial and follow-up procedures.

10. Be able to understand the nature of the trial and complete the written informed consent form.

Exclusion Criteria

1. Rare EGFR mutations;

2. Prior treatment with pemetrexed and platinum-based chemotherapy regimens;

3. Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases;

4. Active hepatitis B (serum HBV DNA ≥10⁴ copies/mL [i.e., 20,000 IU/mL]), hepatitis C virus antibody positive, HIV antibody positive, or treponema pallidum antibody positive;

5. Women of childbearing potential with a positive serum pregnancy test within 7 days prior to treatment initiation, pregnant or lactating women, or male and female subjects not using effective contraception or planning pregnancy during treatment and for 3 months post-treatment;

6. Patients who used or require concomitant use of the following drugs within 14 days prior to the first dose or during treatment: drugs associated with QTc prolongation and/or risk of torsades de pointes ventricular tachycardia; strong CYP3A inhibitors or inducers;

7. Patients who underwent major surgery or immunotherapy within 4 weeks prior to the first dose; patients who received radiotherapy within 2 weeks prior to the first dose.

8. Imaging (CT or MRI) demonstrating tumor invasion of major vessels, or a high likelihood of tumor invasion into critical vessels causing fatal hemorrhage during the study period;

9. History of interstitial lung disease, drug-induced interstitial disease, or any clinically evident active interstitial lung disease; presence of idiopathic pulmonary fibrosis identified on baseline CT scan;

10. Other severe acute or chronic medical conditions, including uncontrolled diabetes, medical or psychiatric disorders, or laboratory abnormalities, that in the investigator's judgment may increase study-related risks or interfere with interpretation of study results;

11. Other conditions deemed by the investigator to be unsuitable for participation in this trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Betta Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

XiaoFeng Pei

Role: STUDY_DIRECTOR

The Fifth Affliated Hospital, Sun Yat-sen University

YingNi Lian

Role: PRINCIPAL_INVESTIGATOR

The First People's Hospital of Zhaoqing

DongYing Liu

Role: PRINCIPAL_INVESTIGATOR

Jiangmen Central Hospital

GuiNan Lin

Role: PRINCIPAL_INVESTIGATOR

Zhongshan People's Hospital, Guangdong, China

Shaodong Hong

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shaodong Hong

Role: CONTACT

hongshd@sysucc.org.cn

15920527656

Facility Contacts

Shao dong Hong

Role: primary

hongshd@sysucc.org.cn

15920527656

Xiaofeng Pei

Role: primary

peixf3@mail.sysu.edu.cn

+86 139 2338 1037

Other Identifiers

BD-BF-IV028

Identifier Type: -

Identifier Source: org_study_id