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

NCT07181499 | Recruiting Phase 2

• 1 other identifier: BD-BF-IV028
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• progression free survival

  It refers to the time from the start of treatment until the tumor progresses or until death occurs for any reason (whichever occurs first).

  From enrollment to the end of treatment at 12 months

Secondary Outcomes (4)

• objective remission rate

  From enrollment to the end of treatment at 12 month

• Disease control rate

  From enrollment to the end of treatment at 12 months

• overall survival

  From enrollment to the end of treatment at 36 months

• adverse event

  From enrollment to the end of treatment at 12 months

Study Arms (1)

Group 1

EXPERIMENTAL

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

Drug: Befotertinib; Drug: Pemetrexed + Carboplatin

Interventions

Befotertinib 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.

Group 1

Pemetrexed + Carboplatin DRUG

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

Group 1

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years;
• 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);
• ECOG performance status (PS) score of 0-2;
• Life expectancy of at least 12 weeks;
• Ability to swallow oral medications;
• Adequate organ system function, defined as follows and determined based on investigator judgment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
• Platelets ≥ 100 x 10⁹/L;
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L). Note: Blood transfusions are permitted to achieve the required hemoglobin level;
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• If no liver metastases: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if liver metastases present: ≤ 5 × ULN;
• 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);
• 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.
• Voluntarily agree and be capable of adhering to the trial and follow-up procedures.
• Be able to understand the nature of the trial and complete the written informed consent form.

You may not qualify if:

• Rare EGFR mutations;
• Prior treatment with pemetrexed and platinum-based chemotherapy regimens;
• Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases;
• 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;
• 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;
• 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;
• 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.
• 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;
• 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;
• 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;
• Other conditions deemed by the investigator to be unsuitable for participation in this trial.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

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

Zhuhai, Guangdong, China

RECRUITING

MeSH Terms

Interventions

Pemetrexed; Carboplatin

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; Coordination Complexes; Organic Chemicals

Study Officials

• XiaoFeng Pei

  The Fifth Affliated Hospital, Sun Yat-sen University

  STUDY DIRECTOR

• YingNi Lian

  The First People's Hospital of Zhaoqing

  PRINCIPAL INVESTIGATOR

• DongYing Liu

  Jiangmen Central Hospital

  PRINCIPAL INVESTIGATOR

• GuiNan Lin

  Zhongshan People's Hospital, Guangdong, China

  PRINCIPAL INVESTIGATOR

• Shaodong Hong

  Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Shaodong Hong

CONTACT

15920527656; hongshd@sysucc.org.cn

Study Design

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

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 18, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

CN (2)