Adjuvant Befotertinib in Stage IB-IIIB Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations

NCT06041776 | Recruiting Phase 3 DMC

• 1 other identifier: BD-BF-III01
• Study Type: interventional
• Target: 570
• Locations: 1 country
• Sites: 3

Brief Summary

This multicenter, randomized, controlled, double-blind, double-simulated, Phase III study is designed to evaluate the efficacy and safety of Befotertinib compared with Icotinib as adjuvant treatment in EGFR-sensitive mutation-positive stage IB-IIIB (T3N2M0) non-small cell lung cancer after surgical resection.

Conditions

Non-Small Cell Lung Cancer; EGFR Sensitive Mutation; Adjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Disease free survival (DFS) evaluated by investigator in patients with stage II-IIIB (T3N2M0)

  up to 5 years

Secondary Outcomes (1)

• DFS evaluated by investigator in patients with stage IB-IIIB (T3N2M0)

  up to 5 years

Other Outcomes (6)

• DFS rate at 2 years

  Assessed at 2 years

• DFS rate at 3 years

  Assessed at 3 years

• DFS rate at 5 years

  Assessed at 5 years

Study Arms (2)

Befotertinib + Icotinib placebo

EXPERIMENTAL

Befotertinib (75 mg or 100 mg orally, once daily) and Icotinib placebo(125 mg orally, three times daily)，in accordance with the randomization schedule

Drug: Befotertinib + Icotinib placebo

Icotinib + Befotertinib placebo

ACTIVE COMPARATOR

Icotinib (125 mg orally, three times daily) and Befotertinib placebo (75 mg or 100 mg orally, once daily)，in accordance with the randomization schedule

Drug: Icotinib + Befotertinib placebo

Interventions

Befotertinib + Icotinib placebo DRUG

The initial dose of Befotertinib is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days. Befotertinib can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis) Icotinib placebo 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).

Befotertinib + Icotinib placebo

Icotinib + Befotertinib placebo DRUG

Icotinib 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis). The initial dose of Befotertinib placebo is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days. Befotertinib placebo can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis.

Icotinib + Befotertinib placebo

Eligibility Criteria

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

You may qualify if:

• Willingness to sign informed consent prior to any study specific procedures, and ability to with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Male or female, aged at least 18 years.
• Histologically confirmed primary NSCLC, and mainly non-squamous cell carcinoma (including mixed type carcinoma mainly composed of adenocarcinoma components).
• Absence of brain metastasis.
• Complete resection of histologically confirmed Stage IB, II, IIIA or IIIB(T3N2M0) according to the TNM staging system for lung cancer (AJCC/UICC 8th edition), with negative margins.
• Confirmation by the central laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
• Patients who fully recover from surgery during randomization (any surgery must achieve complete postoperative wound healing) and should receive adjuvant treatment within 4-10 weeks after surgery.
• ECOG-PS score of 0 or 1 and did not deteriorate 2 weeks before the first administration of the investigational drug, with a minimum expected survival greater than 12 weeks.
• Female subjects with fertility need to have a negative serum pregnancy test during screening.
• Female subjects who have possibility of becoming pregnant, as well as male subjects whose partners are women of childbearing age, must use a highly effective contraceptive method (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) throughout the study and continue to use contraception for 3 months after the end of treatment.

You may not qualify if:

• There are unresectable or metastatic diseases, pathological reports showing positive surgical margins under the microscope or extranodal invasion, or lesions left after surgery, or suspicious lesions determined by imaging after surgery. Subjects receiving only wedge resection.
• Upper lung groove cancer.
• Patient with complete resection of the right lung with NSCLC.
• Malignancies other than NSCLC within 5 years prior to first dosage, except for malignant tumors that can be cured after treatment (including but not limited to fully treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or breast ductal carcinoma in situ treated with radical surgery).
• Received systematic anti-tumor therapy, including chemotherapy, radiotherapy or targeted therapy (including but not limited to monoclonal antibodies, small molecule tyrosine kinase inhibitors), immunotherapy, investigational therapy, etc., before being enrolled in this study.
• Within 3 weeks prior to the first administration of the investigational drug, the patient underwent major surgery (including primary tumor surgery, craniotomy, thoracotomy, or laparotomy, excluding vascular pathway establishment procedures).
• Within 14 days prior to first dose of the investigational drug, Traditional Chinese medicine with anti-tumor indications have been received.
• After the start of the study, any form of systemic or local anti-tumor treatment (including maintenance therapy with another drug, radiotherapy, and/or surgical resection) is still required.
• Clinically significant cardiovascular diseases, including:
• QTcF interval \>450 ms (men) or \>470 ms (women), symptomatic bradycardia (\<45 beats /min), or other significant ECG abnormalities as determined by the investigator (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250 msec).
• Echocardiography showed LVEF \<50%.
• Hypertension was clinically uncontrollable (e.g., blood pressure \>160/100 mmHg; Except that isolated elevated readings that were determined by the investigators to be clinically insignificant or controllable hypertension.)
• Within 6 months before the first medication, there were the following situations:
• Congestive heart failure (New York Heart Association rating III or IV).
• Arrhythmias or conduction abnormalities that require medication treatment. Note: Patients with drug-controlled atrial fibrillation/flutter, as well as those with pacemaker- controlled arrhythmia, can be selected.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (3)

Peking University International Hospital

Beijing, China

RECRUITING

Jiangsu Cancer Hospital

Nanjing, China

RECRUITING

Shanghai chest hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

icotinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Shun Lu, M.D.

  Shanghai Chest Hospital

  STUDY CHAIR

Central Study Contacts

Shun Lu, M.D.

CONTACT

+86 21 2220 0000; shunlu@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 18, 2023
• Study Start: March 28, 2023
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: September 22, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)