Keynatinib in Treated Patients With NSCLC and Brain Metastases

NCT ID: NCT04824079

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-21
• Study Completion Date: 2024-12-10

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Keynatinib capsules in patients with advanced non-small cell lung cancer (NSCLC) with brain metastasis or progression of brain metastasis after treatment with EGFR inhibitors. As well as, to evaluate the penetration rate of Keynatinib in the Blood-Brain Barrier (BBB) and its PK characteristics, and the relationship between exposure levels with efficacy and safety.

Detailed Description

This is a multicenter, non-randomized, open, single-arm, phase IIa trial investigating the security and effectiveness of Keynatinib in patients with advanced non-small cell lung cancer (NSCLC) with brain metastasis or progression of brain metastasis after treatment with EGFR inhibitors.

Conditions

Non-Small Cell Lung Cancer With EGFR Mutation; Brain Metastases

Study Design

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

Study Groups

Keynatinib treatment group

All subjects shall be treated with Keynatinib twice a day (once every 12±3 hours), 20 mg each time, fasting within 2 hours before and 1 hour after taking the drug, and taking warm water when taking the drug. Every 21 days is a treatment cycle .

Group Type: EXPERIMENTAL

Keynatinib

Intervention Type: DRUG

The recommended dose is 20 mg Keynatinib twice a day until disease progression， unacceptable toxicity death occurs or withdraw from the study, whichever occurs first.

Interventions

Keynatinib

The recommended dose is 20 mg Keynatinib twice a day until disease progression， unacceptable toxicity death occurs or withdraw from the study, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

TL007

Eligibility Criteria

Inclusion Criteria

1. Unlimited gender, age ≥ 18 years；

2. Histologically or cytologically documented locally advanced, metastatic NSCLC (including L858R and/or Exon19 del mutation positive). The EGFR mutation assessed by local laboratory/or central laboratory via tissue/cytology or in plasma;

3. Subjects should have the following conditions: a. (Cohort 1) Progression on any of the first or second generation EGFR inhibitors (gefitinib, erlotinib, afatinib, etc.).B. (Cohort 2) Progression on any third generation EGFR inhibitor (oxitinib, etc.), prior or non-prior treatment with any first or second generation EGFR inhibitor;

4. The peripheral lesions did not progress after EGFR inhibitor treatment, but the occurrence of brain metastasis or progression of brain metastasis was confirmed by magnetic resonance imaging (MRI);

5. As determined by the investigator, no final surgical resection or radiotherapy is expected for all lesions;

6. Stable condition for at least 2 weeks prior to study medication without any corticosteroid or anticonvulsant therapy;

7. The status score of Eastern Cooperative Oncology Group (ECOG) is 0 to 1 points, and there was no deterioration during the first 2 weeks of enrollment;

8. Estimated survival time > 3 months；

9. Sufficient bone marrow, liver, kidney and blood coagulation function；

10. Subjects must be willing to use barrier contraception；

11. Ability to provide informed consent, complete all study assessments and have complete medical record.

Exclusion Criteria

1. Have previously received chemotherapy, immunotherapy or any other systemic antitumor therapies within 4 weeks before the first administration; Have previously received EGFR-TKI within 5× half-life before the first administration; Have received oral fluorouracil and other small-molecule targeted drugs (whichever is longer) within 2 weeks or 5× half-life before enrollment; Within 2 weeks before enrollment, subjects had received palliative radiotherapy for non-target lesions for symptom relief, and traditional Chinese medicine (including Chinese patent medicine) for tumor indication;

2. Have received whole brain radiation therapy;

3. Only leptomeningeal metastasis are present;

4. Historical intracranial hemorrhage not related to the tumor;

5. Major organ surgery (excluding needle biopsy) or significant trauma have been performed within 4 weeks prior to enrollment;

6. The drug or food with strong inhibition or induction of cytochrome P450 (CYP) isoenzyme CYP3A4 could not be stopped. The drug or food with strong inhibition or induction of cytochrome P450 (CYP) isoenzyme CYP3A4 had been used within 7 days before enrollment;

7. Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1 at the time of enrollment with the exception of alopecia;

8. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the tablet or previous significant bowel resection that would preclude adequate absorption of Keynatinib;

9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or CT scan at baseline revealed the presence of idiopathic pulmonary fibrosis; Uncontrolled large pleural effusion or pericardial effusion; Active tuberculosis;

10. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or active infection including hepatitis B, hepatitis C and HIV;

11. Have a history of severe cardiovascular disease (NYHA cardiac function grade III or IV);

12. Other primary malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within 5 years;

13. Allergic to the active ingredient or excipient of Keynatinib;

14. Pregnant or lactating women.

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

Sponsors

Medolution Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Fujian Cancer Hospital

Fuzhou, Fujian, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Shandong Cancer Hospital

Jinan, Shandong, China

Countries

China

Other Identifiers

MEDO-007-20002

Identifier Type: -

Identifier Source: org_study_id