AP-L1898 Capsule in Patients With Non-small Cell Lung Cancer

NCT04993391 | Unknown Phase 1

• 1 other identifier: JS111-001-I
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 37

Brief Summary

This is a phase I/II, open-label, first-in-human clinical study designed to evaluate the safety, tolerability, PK profile and efficacy of JS111 for patients with Non-small cell lung cance. This study is divided into 3 periods: dose escalation stage, dose extension stage, and efficacy extension stage.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (6)

• Safety assessed by the adverse event

  The AEs summary will be provided.

  up to 3 years

• Safety assessed by the serious adverse event

  The SAEs summary will be provided.

  up to 3 years

• Safety assessed by the physical examinatin

  The abnormal physical examinatin summary will be provided.

  up to 3 years

• Safety assessed by the ECOG score

  The worsening ECOG score summary will be provided.

  up to 3 years

• Safety assessed by the ophthalmic examination

  The ophthalmic examination summary will be provided.

  up to 3 years

• ORR

  The ORR summary will be calculated.

  up to 3 years

Secondary Outcomes (10)

• Cmax

  0up to 3 years

• Tmax

  up to 3 years

• AUC 0-t

  up to 3 years

• t1/2

  up to 3 years

• CL/F

  up to 3 years

Study Arms (5)

40mg dose.

EXPERIMENTAL

The subjects will receive a single dose at first in this stage, and be observed for 7 days subsequently, if tolerated, the subjects will enter the multi-dose study on oral AP-L1898 once per day for consecutive 21 days. The DLT observational per

Drug: JS111(AP-L1898 Capsules)

80mg dose.

EXPERIMENTAL

The subjects will receive a single dose at first in this stage, and be observed for 7 days subsequently, if tolerated, the subjects will enter the multi-dose study on oral AP-L1898 once per day for consecutive 21 days. The DLT observational per

Drug: JS111(AP-L1898 Capsules)

160mg dose.

EXPERIMENTAL

The subjects will receive a single dose at first in this stage, and be observed for 7 days subsequently, if tolerated, the subjects will enter the multi-dose study on oral AP-L1898 once per day for consecutive 21 days. The DLT observational pe

Drug: JS111(AP-L1898 Capsules)

240mg dose.

EXPERIMENTAL

The subjects will receive a single dose at first in this stage, and be observed for 7 days subsequently, if tolerated, the subjects will enter the multi-dose study on oral AP-L1898 once per day for consecutive 21 days. The DLT observational pe

Drug: JS111(AP-L1898 Capsules)

320mg dose.

EXPERIMENTAL

The subjects will receive a single dose at first in this stage, and be observed for 7 days subsequently, if tolerated, the subjects will enter the multi-dose study on oral AP-L1898 once per day for consecutive 21 days. The DLT observational pe

Drug: JS111(AP-L1898 Capsules)

Interventions

JS111(AP-L1898 Capsules) DRUG

40 mg, QD

40mg dose.

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, male or female;
• Patients with histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC that can not undergo radical chemoradiotherapy;
• Dose-escalation and dose-extension periods: failure of standard of care or intolerance of standard of care, having received at least one or more systemic therapeutic regimens for locally advanced or metastatic disease;
• There is clear evidence showing carrying EGFR exon 20 insertion and other rare EGFR mutations (only applicable for dose-extension and efficacy-extension periods). The test method can use: ARMS method for tissue or cell specimen (need to be tested in national certified laboratory), NGS method for tissue or blood specimen (need to be tested in CLIA or CAP certified laboratory). Note: enrollment of patients does not need to be confirmed by central laboratory;
• At least one measurable lesion meeting RECIST v1.1 definition, no history of puncture biopsy for the target lesion within the previous two weeks;
• United States Eastern Cooperative Oncology Group (ECOG) Performance Status score 0\~1;
• Life expectancy \>12 weeks;
• Having adequate function of important organs at screening (requiring no blood transfusion, no use of hematopoietic stimulating factor or human albumin preparation within 14 days prior to screening):
• Absolute neutrophil count (ANC) ≥1.5x109/L;
• Platelets ≥100×109/L;
• Haemoglobin \> 90 g/L;
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5×upper limit of normal (ULN) (for known liver metastasis, ≤ 5×ULN);
• Total bilirubin ≤1.5×ULN;
• Coagulation function INR≤1.5 ULN;
• Serum creatinine ≤ 1.5×ULN or creatinine clearance (Ccr, calculated using Cockcroft-Gault formula) ≥45 mL/min;

You may not qualify if:

• Use of any chemotherapeutic agen within 14 days prior to the first dose of AP-L1898; or the time from discontinuation of other investigational product to the use of anticancer drug less than 5 half-lives or 28 days, whichever is shorter;
• EGFR exon 20 insertion cohort in efficacy-extension stage: once used the drugs targeting EGFR exon 20 insertion mutation (e.g., AZD9291, TAK-788, Poziotinib, CLN-081, JNJ-372, etc.); the patients previously receiving AZD9291 for treatment of EGFR sensitive mutation are allowed to be enrolled;
• Ongoing use of CYP3A potent inhibitor or inducer, or discontinuation of potent inhibitor less than 5 half-lives of the drug, or discontinuation of potent inducer less than 5 half-lives of the drug or 14 days (whichever is longer) at the first dose of AP-L1898;
• Not recovered from the adverse event induced by previous antitumor therapy at screening (recovered to ≤ grade 1) (except alopecia);
• Having other malignant tumors within 5 years prior to the start of treatment or simultaneously (except radically treated non-melanoma without evidence on recurrence of disease, including skin basal cell carcinoma or squamous cell carcinoma, breast/cervical carcinoma in situ, superficial bladder cancer and other carcinomas in situ);
• Presence of active gastrointestinal disease or other conditions that may obviously affect absorption, metabolism or excretion of drugs;
• Patients who known to have received organ transplantation;
• Major surgery performed within 28 days prior to the first dose. Small surgery permitted, e.g., minimally invasive biopsy;
• Patents with carcinomatous meningitis, spinal cord compression at present;
• At rested state, mean corrected QT interval QTc, using Fridericia's correction formula\>450 ms in man or \>470 ms in woman on electrocardiography (ECG) (repeated for three times). A variety of clinically significant abnormalities in cardiac rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, degree III heart block, degree II heart block, PR interval\>250 ms. Any factors that may increase the risk of prolonged QTc interval or risk of arrhythmic events, e.g., heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in lineal relatives, or ongoing use of any drug known to prolong QT interval;
• History of poorly controlled hypertension;
• Previous history of the following diseases: interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, active interstitial lung disease with clinical evidence;
• Patients with active brain metastasis, if the CNS metastasis is only limited to supratentorial area or cerebellum that has been adequately treated (surgery or radiotherapy) and radiologically stable for at least 4 weeks, and no corticosteroid is needed to control symptoms, the patients will be allowed to be enrolled;
• In acute infection phase and requiring pharmacotherapy;
• HBV DNA≥103 copies/mL or ≥200 IU/mL when the hepatitis B surface antigen is positive or hepatitis B core antibody is positive;

Sponsors & Collaborators

• Suzhou Junjing BioSciences Co., Ltd.: lead

Study Sites (37)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

NOT YET RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

NOT YET RECRUITING

Chinese People's Liberation Army Army Characteristic Medical Center

Chongqing, Chongqing Municipality, 400042, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350001, China

NOT YET RECRUITING

Sun Yat-sen Memorial Hospital ], Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510163, China

NOT YET RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences，Shenzhen center

Shenzhen, Guangdong, 518116, China

NOT YET RECRUITING

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, 524023, China

NOT YET RECRUITING

Liuzhou People's Hospital

Liuchow, Guangxi, 545006, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital

Haerbin, Heilongjiang, 150081, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430023, China

NOT YET RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

NOT YET RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

NOT YET RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

NOT YET RECRUITING

North Jiangsu People's Hospital

Yangzhou, Jiangsu, 225001, China

NOT YET RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

NOT YET RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

NOT YET RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

NOT YET RECRUITING

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

NOT YET RECRUITING

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Neimenggu, 010050, China

NOT YET RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

NOT YET RECRUITING

Weifang People's Hospital

Weifang, Shandong, 261000, China

NOT YET RECRUITING

Shanghai Oriental Hospital

Shanghai, Shanghai Municipality, 200127, China

NOT YET RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710061, China

NOT YET RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650106, China

NOT YET RECRUITING

Hangzhou Cancer Hospital

Hangzhou, Zhejiang, 310002, China

NOT YET RECRUITING

The First Affiliated Hospital , Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

NOT YET RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

NOT YET RECRUITING

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

NOT YET RECRUITING

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang, 317000, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, China

NOT YET RECRUITING

Shanghai Pulmonary Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Lina Qin

CONTACT

86 18600672907; lina_qin@junshipharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: August 6, 2021
• Study Start: July 13, 2021
• Primary Completion: June 18, 2024
• Study Completion: August 18, 2024
• Last Updated: October 26, 2022

Record last verified: 2022-08

Locations

CN (37)