Clinical trial NCT04993391: AP-L1898 Capsule in Patients With Non-small Cell Lung Cancer
Official title: A Dose-escalation, Dose-extension and Efficacy-extension, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of AP-L1898 Capsule for the Treatment of the Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Lead sponsor: Suzhou Junjing BioSciences Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. Age≥18 years, male or female;
2. Patients with histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC that can not undergo radical chemoradiotherapy;
3. 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;
4. 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;
5. At least one measurable lesion meeting RECIST v1.1 definition, no history of puncture biopsy for the target lesion within the previous two weeks;
6. United States Eastern Cooperative Oncology Group (ECOG) Performance Status score 0\~1;
7. Life expectancy \>12 weeks;
8. 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):

   1. Absolute neutrophil count (ANC) ≥1.5x109/L;
   2. Platelets ≥100×109/L;
   3. Haemoglobin \> 90 g/L;
   4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5×upper limit of normal (ULN) (for known liver metastasis, ≤ 5×ULN);
   5. Total bilirubin ≤1.5×ULN;
   6. Coagulation function INR≤1.5 ULN;
   7. Serum creatinine ≤ 1.5×ULN or creatinine clearance (Ccr, calculated using Cockcroft-Gault formula) ≥45 mL/min;
   8. Serum lipase and amylase ≤ 1.5 × ULN;
9. Serum pregnancy test must be confirmed as negative for women of childbearing potential within 7 days prior to enrollment, who agree upon use of effective contraceptive measures during use of the study drug and within 6 months after the last dose. Women of childbearing potential in this protocol is defined as sexually mature women: 1) no hysterectomy or bilateral ovariectomy, 2) uncontinuous natural menopause for 24 months (i.e., menses occurred at any time in the previous consecutive 24 months; fertility can not be excluded in case of amenorrhoea following cancer therapy). Male subjects whose partners are women of childbearing potential must agree to take effective contraceptive measures during the use of study drug and within 6 months after the last dose;
10. Being voluntary to participate in this study after sufficient informed consent and sign the informed consent form.

Exclusion criteria:

1. 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;
2. 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;
3. 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;
4. Not recovered from the adverse event induced by previous antitumor therapy at screening (recovered to ≤ grade 1) (except alopecia);
5. 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);
6. Presence of active gastrointestinal disease or other conditions that may obviously affect absorption, metabolism or excretion of drugs;
7. Patients who known to have received organ transplantation;
8. Major surgery performed within 28 days prior to the first dose. Small surgery permitted, e.g., minimally invasive biopsy;
9. Patents with carcinomatous meningitis, spinal cord compression at present;
10. 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;
11. History of poorly controlled hypertension;
12. 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;
13. 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;
14. In acute infection phase and requiring pharmacotherapy;
15. HBV DNA≥103 copies/mL or ≥200 IU/mL when the hepatitis B surface antigen is positive or hepatitis B core antibody is positive;
16. HCV-RNA \> the upper limit of reference at the site when hepatitis C antibody is positive;
17. Human immunodeficiency virus (HIV) antibody positive;
18. Patient with a previous history of clear mental disorder and taking drugs for treatment;
19. Patient with a history of drug abuse or drug taking;
20. Pregnant or lactating women;
21. Presence of other factors that may possibly affect the study results, interfere with their participation in the entire study, including previous or current physical condition (e.g., ocular disease, including corneal ulcer, conjunctivitis, etc.), treatment or laboratory examination abnormality, unwillingness to comply with each procedure, restriction and requirement in the study, as considered by investigators.

A limited list of criteria for selection of participants in the clinical study, provided in terms of inclusion and exclusion criteria and suitable for assisting potential participants in identifying clinical studies of interest. Use a bulleted list for each criterion below the headers "Inclusion Criteria" and "Exclusion Criteria". (Limit: 15,000 characters.)

Primary outcomes:
measure: Safety assessed by the adverse event
timeFrame: up to 3 years
measure: Safety assessed by the serious adverse event
timeFrame: up to 3 years
measure: Safety assessed by the physical examinatin
timeFrame: up to 3 years
measure: Safety assessed by the ECOG score
timeFrame: up to 3 years
measure: Safety assessed by the ophthalmic examination
timeFrame: up to 3 years
measure: ORR
timeFrame: up to 3 years
Secondary outcomes:
measure: Cmax
timeFrame: 0up to 3 years
measure: Tmax
timeFrame: up to 3 years
measure: AUC 0-t
timeFrame: up to 3 years
measure: t1/2
timeFrame: up to 3 years
measure: CL/F
timeFrame: up to 3 years
measure: Vd/F
timeFrame: up to 3 years
measure: DoR
timeFrame: up to 3 years
measure: OS
timeFrame: up to 3 years
measure: DCR
timeFrame: up to 3 years
measure: Plasma drug concentration after administration of study drug
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chinese People's Liberation Army Army Characteristic Medical Center
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital ], Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences，Shenzhen center
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Yangzhou
country: China
facility: North Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Huhehaote
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Neimenggu
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Hangzhou Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital , Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
References: