## Protocol Section
### Identification Module
**NCT ID:** NCT04824079

**Brief Title:** Keynatinib in Treated Patients With NSCLC and Brain Metastases

**Official Title:** Study of Keynatinib in Patients With Advanced Non-small Cell Lung Cancer With Brain Metastasis or Progression of Brain Metastasis After Treatment With EGFR Inhibitor(s)

#### Organization Study ID Info
**ID:** MEDO-007-20002
#### Organization
**Class:** INDUSTRY
**Full Name:** Medolution Ltd.
### Status Module
#### Completion Date
**Date:** 2025-07-22

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-11-07

**Type:** ACTUAL

**Last Update Submit Date:** 2023-11-04

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-04-22

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-10-21

**Type:** ACTUAL

**Status Verified Date:** 2023-11

#### Study First Post Date
**Date:** 2021-04-01
**Type:** ACTUAL
**Study First Submit Date:** 2021-03-23
**Study First Submit QC Date:** 2021-03-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Medolution Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Non-Small Cell Lung Cancer With EGFR Mutation

- Brain Metastases

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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 .

**Intervention Names:**

- Drug: Keynatinib

**Label:** Keynatinib treatment group

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Keynatinib treatment group

**Description:** 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.

**Name:** Keynatinib

**Other Names:**

- TL007

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** Objective Response Rate

**Time Frame:** 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.

### Eligibility Module

**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 Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** syuankaipumc@126.com

- **Name:** Yuankai Shi, PhD

- **Phone:** +86(010)-87788293

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yuankai Shi, phD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 3:***

- **Name:** Shengyu Zhou, phD

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Cancer Hospital, Chinese Academy of Medical Sciences

**State:** Beijing

**Status:** NOT_YET_RECRUITING

**Zip:** 100021

**Location 2:**

**City:** Fuzhou

**Contacts:**

***Contact 1:***

- **Email:** Zhuangwu2008@126.com

- **Name:** Wu Zhuang, phD

- **Phone:** +8613809500871

- **Role:** CONTACT

***Contact 2:***

- **Name:** Wu Zhuang, phD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Fujian Cancer Hospital

**State:** Fujian

**Status:** NOT_YET_RECRUITING

**Zip:** 350014

**Location 3:**

**City:** Zhengzhou

**Contacts:**

***Contact 1:***

- **Email:** 13838528387@163.com

- **Name:** Huijuan Wu, MD

- **Phone:** +8613838528387

- **Role:** CONTACT

***Contact 2:***

- **Name:** Huijuan Wu, MD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 3:***

- **Name:** Yanqiu Zhao, MD

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Henan Cancer Hospital

**State:** Henan

**Status:** RECRUITING

**Zip:** 450003

**Location 4:**

**City:** Changsha

**Contacts:**

***Contact 1:***

- **Email:** cjh_1000@163.com

- **Name:** Jianhua Chen, MD

- **Phone:** +8613807488036

- **Role:** CONTACT

***Contact 2:***

- **Name:** Jianhua Chen, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Hunan Cancer Hospital

**State:** Hunan

**Status:** RECRUITING

**Zip:** 410013

**Location 5:**

**City:** Jinan

**Contacts:**

***Contact 1:***

- **Email:** guoqs369@163.com

- **Name:** Qisen Guo, phD

- **Phone:** +8613869199681

- **Role:** CONTACT

***Contact 2:***

- **Name:** Qisen Guo, phD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Shandong Cancer Hospital

**State:** Shandong

**Status:** RECRUITING

**Zip:** 250000

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

- ID: D000009385

- Term: Neoplastic Processes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000016543

- Term: Central Nervous System Neoplasms

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC10

- Name: Nervous System Diseases

### Condition Browse Module - Browse Leaves

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Cancer

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Cancer

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: HIGH

- As Found: Metastases

- ID: M20559

- Name: Disease Progression

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5209

- Name: Brain Neoplasms

- Relevance: HIGH

- As Found: Brain Metastases

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12330

- Name: Neoplastic Processes

- Relevance: LOW

- As Found: Unknown

- ID: M18937

- Name: Central Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

- ID: D000009362

- Term: Neoplasm Metastasis

- ID: D000001932

- Term: Brain Neoplasms

### Misc Info Module

- Version Holder: 2024-05-24
