Keynatinib in Treated Patients With NSCLC and Brain Metastases

NCT04824079 | Completed Phase 2

• 1 other identifier: MEDO-007-20002
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The proportion of subjects whose optimal efficacy observed from the beginning of administration is CR or PR.

  From start of treatment to time of progression (in CNS or non-CNS disease) , intolerable toxicity, withdrawal of informed consent or death, whichever occurs first，assessed up to 2 years.

Study Arms (1)

Keynatinib treatment group

EXPERIMENTAL

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 .

Drug: Keynatinib

Interventions

Keynatinib 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.

Also known as: TL007

Keynatinib treatment group

Eligibility Criteria

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

You may qualify if:

• Unlimited gender, age ≥ 18 years；
• 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;
• 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;
• 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);
• As determined by the investigator, no final surgical resection or radiotherapy is expected for all lesions;
• Stable condition for at least 2 weeks prior to study medication without any corticosteroid or anticonvulsant therapy;
• 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;
• Estimated survival time \> 3 months；
• Sufficient bone marrow, liver, kidney and blood coagulation function；
• Subjects must be willing to use barrier contraception；
• Ability to provide informed consent, complete all study assessments and have complete medical record.

You may not qualify if:

• 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;
• Have received whole brain radiation therapy;
• Only leptomeningeal metastasis are present;
• Historical intracranial hemorrhage not related to the tumor;
• Major organ surgery (excluding needle biopsy) or significant trauma have been performed within 4 weeks prior to enrollment;
• 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;
• Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1 at the time of enrollment with the exception of alopecia;
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the tablet or previous significant bowel resection that would preclude adequate absorption of Keynatinib;
• 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;
• 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;
• Have a history of severe cardiovascular disease (NYHA cardiac function grade III or IV);
• Other primary malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within 5 years;
• Allergic to the active ingredient or excipient of Keynatinib;
• Pregnant or lactating women.

Sponsors & Collaborators

• Medolution Ltd.: lead

Study Sites (5)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

Shandong Cancer Hospital

Jinan, Shandong, 250000, China

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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: March 23, 2021
• First Posted: April 1, 2021
• Study Start: October 21, 2020
• Primary Completion: December 10, 2024
• Study Completion: December 10, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)