A Phase I/II Clinical Study of SAF-189s in Non-small Cell Lung Cancer (NSCLC) Patients

July 7, 2021 updated by: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

A Phase I/II, Multi-center Clinical Study: Dose-finding Phase I Study of Foritinib Succinate in Advanced ALK-positive NSCLC Patients and Phase II Study of Foritinib Succinate in ALK or ROS1-positive NSCLC Patients

The study comprises two phases: phase I dose escalation (including PK run-in period and treatment period) and phase II study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, single-arm, open-label dose-finding phase I/II study to determine the MTD and RP2D of oral foritinib succinate monotherapy in patients with advanced ALK-positive malignant solid tumor, and to evaluate the safety, tolerability, and PK characteristics of SAF-189s in patients with advanced ALK-positive NSCLC. Phase II clinical study was conducted to evaluate the efficacy, tumor activity, and safety of remitinib succinate in patients with ALK/ROS1 positive advanced non-small cell lung cancer, and to preliminary evaluate the population pharmacokinetic characteristics of remitinib succinate.

This study consisted of two phases: phase I (including PK induction and continuous administration) and phase II, Phase I dose escalation : the patients with advanced ALK-positive malignant solid tumor who have progressed on standard therapies; Phase I study: histologically or cytologically confirmed, locally advanced ALK-positive and/or metastatic stage IIIB/IV NSCLC who have progressed on standard therapy; Phase II Study Part I: Patients with histologically and/or cytologically confirmed ALK or ROS1 positive locally-advanced and/or metastatic stage IIIb ~IV NSCLC;Patients who had not previously received or had received only one ALK/ROS1 inhibitor for disease progression or intolerance, and who had no more than 3 previous treatment lines overall Phase II Study Part Ⅱ: cohort1：ROS1-positive locally advanced and/or metastatic stage IIIB~IV NSCLC patients diagnosed histologically and/or cytologically, with no prior systemic therapy or only one line of non-ROS1-inhibitor treatment cohort 2: patients with histologically and/or cytologically confirmed ROS1-positive locally advanced and/or metastatic stage IIIb ~IV NSCLC who had previously only received crizotinib as a ROS1 inhibitor for disease progression or intolerance and had no more than 3 overall previous treatment lines；

Study Type

Interventional

Enrollment (Anticipated)

280

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Anhui
      • Bengbu, Anhui, China, 233004
        • Recruiting
        • he First Affiliated Hospital of Bengbu Medical College
        • Principal Investigator:
          • Wei Li, Doctor
        • Contact:
    • Beijing
      • Beijing, Beijing, China, 100140
        • Recruiting
        • Peking Union Medical College Hospital
        • Principal Investigator:
          • Li Zhang, Doctor
        • Contact:
      • Beijing, Beijing, China, 100192
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
      • Beijing, Beijing, China, 101149
        • Recruiting
        • Beijing Chest Hospital,Capital Medical University
        • Contact:
        • Principal Investigator:
          • Zhe Liu, Doctor
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:
        • Principal Investigator:
          • Wangjun Wangjun, doctor
      • Guangzhou, Guangdong, China, 510080
        • Recruiting
        • Guangdong Province People's General Hospital
        • Contact:
        • Principal Investigator:
          • Yilong Wu, Doctor
        • Principal Investigator:
          • Jinji Yang, Doctor
      • Shenzhen, Guangdong, China, 518116
        • Recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences, ShenZhen center
        • Contact:
        • Principal Investigator:
          • Shi Shi, Doctor
    • Hebei
      • Baoding, Hebei, China, 071000
        • Recruiting
        • Affiliated Hospital of Hebei University
        • Contact:
        • Principal Investigator:
          • Aimin Zang, master
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • The Fourth Hospital of Hebei Medical University
        • Contact:
        • Principal Investigator:
          • Cuimin Ding, Master
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
        • Principal Investigator:
          • GongYan Chen, Dcotor
    • Henan
      • Zhengzhou, Henan, China, 450014
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
        • Principal Investigator:
          • Mingjun Li, Doctor
      • Zhengzhou, Henan, China, 450052
        • Recruiting
        • Zhengzhou Central Hospital
        • Contact:
        • Principal Investigator:
          • Shanyong Yi, Doctor
      • Zhengzhou, Henan, China, 471003
        • Recruiting
        • The First Affiliated Hospital of Henan University of Science and Technology
        • Contact:
        • Principal Investigator:
          • Zhiye Zhang, Master
        • Principal Investigator:
          • Jiangtao Sun, Doctor
    • Hubei
      • Wuhan, Hubei, China, 430079
        • Recruiting
        • Hubei Cancer Hospital
        • Contact:
          • Yanping Hu, Master
          • Phone Number: 13971385149
          • Email: h-y-p@126.com
        • Principal Investigator:
          • Yanping Hu, Master
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
        • Principal Investigator:
          • Yuan Chen, Doctor
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
        • Principal Investigator:
          • Xiaorong Dong, Doctor
    • Hunan
      • Changsha, Hunan, China, 410006
        • Recruiting
        • Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
        • Contact:
        • Principal Investigator:
          • Nong Yang, Doctor
      • Yongzhou, Hunan, China, 425006
        • Recruiting
        • The Central Hospital of Yongzhou
        • Contact:
          • Pengfei Luo, Master
          • Phone Number: ‭18608462505‬
          • Email: 76756518@qq.com
        • Principal Investigator:
          • Pengfei Luo, Master
    • Jiangsu
      • Nanjing, Jiangsu, China, 225001
        • Recruiting
        • Jiangsu Province Hospital
        • Contact:
        • Principal Investigator:
          • Yongqian Shu, doctor
      • Xuzhou, Jiangsu, China, 221006
        • Recruiting
        • General Hospital of Xuzhou Mining Group
        • Contact:
        • Principal Investigator:
          • Baoqing Wang, Master
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • Recruiting
        • The Second Affiliated Hospital of Nanchang University
        • Contact:
        • Principal Investigator:
          • Anwen Liu, Doctor
    • Jilin
      • Changchun, Jilin, China, 130031
        • Recruiting
        • The First Hospital of Jilin University
        • Contact:
        • Principal Investigator:
          • Jiuwei Cui, Doctor
      • Jilin, Jilin, China, 130021
        • Recruiting
        • Jilin Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Ying Cheng, Bachelor
      • Yanji, Jilin, China, 133000
        • Recruiting
        • Yanbian University Affiliated Hospital
        • Contact:
          • Xionghu Shen, Doctor
          • Phone Number: 15526770368
          • Email: xim918@126.com
        • Principal Investigator:
          • Xionghu Shen, Doctor
    • Liaoning
      • Shenyang, Liaoning, China, 110001
        • Recruiting
        • The First Affiliated Hospital of China Medical University
        • Contact:
        • Principal Investigator:
          • Yunpeng Yunpeng, Doctor
    • Shandong
      • Jinan, Shandong, China, 250013
        • Recruiting
        • Jinan Central Hospital
        • Contact:
        • Principal Investigator:
          • Yuping Sun, Doctor
      • Jinan, Shandong, China, 250031
        • Recruiting
        • No. 960 Hospital of the Joint Service Support Force of Chinese People's Liberation Army
        • Contact:
        • Principal Investigator:
          • Baocheng Wang, Doctor
      • Jinan, Shandong, China, 250061
        • Recruiting
        • Shandong Provincial Qianfoshan Hospital
        • Contact:
        • Principal Investigator:
          • Jun Wang, Doctor
      • Linyi, Shandong, China, 276000
        • Recruiting
        • Linyi Cancer Hospital
        • Contact:
        • Principal Investigator:
          • JianHua Shi, Master
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Recruiting
        • Shanghai Chest Hospital,Shanghai Jiaotong University
        • Contact:
        • Principal Investigator:
          • Liyan Jiang, Doctor
    • Shanxi
      • Jieyang, Shanxi, China, 522000
        • Recruiting
        • Jieyang Peoples Hospital
        • Contact:
        • Principal Investigator:
          • Xiaofen Wang, Bachelor
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital,Sichuan University
        • Contact:
        • Principal Investigator:
          • Ke Wang, Doctor
      • Neijiang, Sichuan, China, 641100
        • Recruiting
        • The Second Peoples Hospital of Neijiang
        • Contact:
        • Principal Investigator:
          • Ou Jiang, Doctor
    • Tianjin
      • Tianjin, Tianjin, China, 300052
        • Recruiting
        • Tianjin Medical University General Hospital
        • Contact:
        • Principal Investigator:
          • Diansheng Zhong, Doctor
      • Tianjin, Tianjin, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Changli Wang, Doctor
      • Tianjin, Tianjin, China, 350000
        • Not yet recruiting
        • Tianjin Peoples Hospital
        • Principal Investigator:
          • Huaqing Wang, Doctor
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Recruiting
        • Zhejiang Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Yun Fan, Doctor
      • Hangzhou, Zhejiang, China, 310014
        • Recruiting
        • Zhejiang provincial people's hospital
        • Contact:
          • Liqin Lu, Bachelor
          • Phone Number: 13858039628
          • Email: llq99@163.com
        • Principal Investigator:
          • Liqin Lu, Bachelor
      • Hangzhou, Zhejiang, China, 310009
        • Recruiting
        • The First Affiliated Hospital, Medical School of Zhejiang University
        • Contact:
          • Jianying Zhou, Doctor
          • Phone Number: +86-0571-87236877
          • Email: drzjy@163.com
        • Principal Investigator:
          • Jianying Zhou, Doctor
      • Hangzhou, Zhejiang, China, 310016
        • Recruiting
        • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
        • Contact:
          • Hongming Pan, Doctor
          • Phone Number: 13605716662
          • Email: shonco@sina.cn
        • Principal Investigator:
          • Hongming Pan, Doctor
    • Zhengjiang
      • Hangzhou, Zhengjiang, China, 310000
        • Recruiting
        • Shulan (Hangzhou) Hospital
        • Contact:
        • Principal Investigator:
          • Qiong Zhao, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1) Have a full understanding of this study and voluntarily sign an informed consent form (ICF) 2）Phase I dose escalation : the patients with advanced ALK-positive malignant solid tumor who have progressed on standard therapies; Phase I study: histologically or cytologically confirmed, locally advanced ALK-positive and/or metastatic stage IIIB/IV NSCLC who have progressed on standard therapy; Phase II Study Part I: Patients with histologically and/or cytologically confirmed ALK or ROS1 positive locally-advanced and/or metastatic stage IIIb ~IV NSCLC;Patients who had not previously received or had received only one ALK/ROS1 inhibitor for disease progression or intolerance, and who had no more than 3 previous treatment lines overall Phase II Study Part Ⅱ: cohort1：ROS1-positive locally advanced and/or metastatic stage IIIB~IV NSCLC patients diagnosed histologically and/or cytologically, with no prior systemic therapy or only one line of non-ROS1-inhibitor treatment cohort 2: patients with histologically and/or cytologically confirmed ROS1-positive locally advanced and/or metastatic stage IIIb ~IV NSCLC who had previously only received crizotinib as a ROS1 inhibitor for disease progression or intolerance and had no more than 3 overall previous treatment lines； 3) At least one measurable lesion per RECIST1.1; Note: a lesion previously treated by radiotherapy is not considered as a target lesion, unless confirmed progression is documented after radiotherapy.

4) ECOG performance score ≤ 2; 5) Male or female patients ≥ 18 and ≤ 75 years old in Phase I ；Male or female patients ≥ 18 in Phase II 6) Life expectancy ≥ 12 weeks; 7) Patient with appropriate organ function as documented by:

  1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
  2. Hemoglobin ≥ 90 g/L;
  3. Platelets (PLT) ≥ 100 × 109/L
  4. Serum total bilirubin ≤ 1.5 × ULN (if the patient has Gilbert's syndrome, ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN);
  5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for patient with liver metastases);
  6. Creatinine clearance (CrCL) ≥ 50 mL/min (calculated by Cockcroft-Gault equation)
  7. Fasting blood glucose ≤ 200 mg/dL (≤ 11.1 mmol/L) 8) Toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 per NCI-CTCAE (Version 4.03), exception of alopecia; 9）Within 21 days prior to enrolment, women of reproductive age had to confirm a negative serological pregnancy test and agree to use an effective contraceptive method for all study drug use and for 28 days after the last dose.For the purposes of this protocol, women of childbearing age are defined as sexually mature women who: 1) have not undergone hysterectomy or bilateral oophorectomy, or 2) have natural menopause that has not lasted continuously for 24 months (amenorrhea after cancer treatment does not exclude fertility) (i.e., have had menstruation at any time during the previous consecutive 24 months);

Exclusion Criteria:

  1. Has had prior chemotherapy, anti-cancer treatment with biological drugs, or other investigational agents within 28 days or received TKI or targeted therapies within 14 days prior to enrollment;
  2. Received radiotherapy within 21 days prior to the 1st dose or continuance of toxicities due to prior radiotherapy that do not recover to Grade 0 or 1;
  3. Patients who received major surgery within 3 weeks before enrollment or have not adequately recovered from prior surgery;

  4. Patients with central nervous system (CNS) metastases requiring

    1. Clinical local intervention such as surgical excision, radiotherapy or other therapies
    2. Phase I dose escalation: patients requiring systemic treatment with corticosteroids (>10 mg/day prednisone or equivalent) are not eligible for dose escalation study (not applicable to patients participating Phase I cohort expansion or Phase II).

  5. Diabetics without stable control and with insulin therapy (patients with fasting blood glucose below 7mmol/L, who are receiving stable hypoglycemic drug regimen, and whose blood glucose control is stable as evaluated by specialist doctors are allowed to be enrolled); 6）Difficulty in swallowing or having an active digestive disorder or having undergone major gastrointestinal surgery may significantly affect the administration or absorption of SAF189s (e.g. ulcerative lesions, uncontrollable nausea, vomiting, diarrhoea, malabsorption syndrome, and enteroctomies) 7）Patients who are taking the following medicines:

    1. Repaglinide (cytochrome [CYP]2C8) and drugs metabolized via CYP3A4 enzyme within 1 week before enrollment;
    2. Medicines which are known to cause QT prolongation or torsade de pointes;
    3. Coumarin anticoagulants within 1 week before enrollment (low molecular weight heparin is permitted);
    4. Illegal drugs;

8) Has a history of acute pancreatitis within 1 year before enrollment, or past history of chronic pancreatitis; 9) Patients have positive laboratory test for anti-HCV, or are diagnosed with human immunodeficiency virus (HIV) infection, or who refuse to receive HIV screen test; 10) Patients have other malignant tumor history or with other malignant tumors simultaneously; 11) Impairment of cardiac function or clinically significant heart disease, including New York College of Cardiology (NYHA) grade ≥ 3 congestive heart failure, arrhythmias, conduction abnormalities requiring treatment, cardiomyopathy, or uncontrolled hypertension； 12) Corrected QT interval using Fridericia formula > 450 msec for male patients and > 470 msec for female patients; 13) Patients have uncured interstitial lung disease history or non-infectious pneumonitis prior to enrollment, except for those induced by radiation therapy; 14）Any other clinically significant disease or condition (such as uncontrolled diabetes, active or uncontrolled infections, etc.) that the investigator believes could affect protocol adherence or affect the patient's ability to sign up for ICF; 15）Spinal cord metastases with potential risk or symptoms of spinal cord compression； 16）The second cohort received ROS1 inhibitors other than crizotinib； 17）The patient had uncontrollable amounts of pleural effusion, ascites, and pericardial effusion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SAF-189s
The phase I dose study will enrol patients with advanced malignant solid tumors that are ALK-positive, and the phase II study will be divided into two parts, Part I Some patients with ALK/ROS1 positive advanced non-small cell lung cancer were enrolled in the 210m,80mg,120mg and 160mg dose groups for safety evaluation.In the second part, two cohorts will be included and 110 ROS1 patients will be enrolled. Except for the PK induction period, all patients will receive oral administration of SAF189s once a day for a continuous period of 21 days.
Drug: SAF-189s
20mg，40mg，80mg，120mg，160mg，210mg，once daily
Other Names:
  • foritinib succinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DLT
Time Frame: 24 days after the first dose in the dose escalation phase
Dose Limiting Toxicity incidence within 24 days after the first dose in the dose escalation phase
24 days after the first dose in the dose escalation phase
ORR
Time Frame: until 6 months' treatment of the last patients in each cohort
Objective response rate
until 6 months' treatment of the last patients in each cohort

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TEAE
Time Frame: through study completion, an average of 3 year
TEAE incidence, types, grade of toxicity according to NCI-CTCAE (version 5.0); study-related TEAE, SAE, study-related SAE, ≥ Grade 3 TEAE, ≥ Grade 3 TESAE, and TEAE leading to permanent discontinuation.
through study completion, an average of 3 year
PFS
Time Frame: 3 years
Progression-free survival (PFS)
3 years
CBR
Time Frame: 3 years
clinical benefit rate (CBR)
3 years
DOR
Time Frame: 3 years
duration of response (DoR)
3 years
OS
Time Frame: 4 years
Overall survival (OS)
4 years
Cmax
Time Frame: 1 years
Maximum Plasma Concentration
1 years
CNS responses
Time Frame: 4 years
Central nervous system efficacy evaluation，（time to CNS progression，CNS TTP），（CNS objective response rate，CNS ORR）,（duration of CNS response，CNS DOR）
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Investigators

  • Principal Investigator: Yilong Wu, Doctor, Guangdong Province People's General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2016

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

March 31, 2026

Study Registration Dates

First Submitted

January 15, 2020

First Submitted That Met QC Criteria

January 18, 2020

First Posted (Actual)

January 23, 2020

Study Record Updates

Last Update Posted (Actual)

July 8, 2021

Last Update Submitted That Met QC Criteria

July 7, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAF001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Solid Tumor

Clinical Trials on SAF-189s

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe