Advanced CancerPhase 1/2NCT04237805
A Phase I/II Clinical Study of SAF-189s in Non-small Cell Lung Cancer (NSCLC) Patients
A Phase 1/2 study testing SAF-189s in people with Advanced Cancer and Advanced Solid Tumor, run by Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. at 41 sites in China.
Trial summary
The study comprises two phases: phase I dose escalation (including PK run-in period and treatment period) and phase II study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Advanced Solid Tumor, Lung Cancer, Nonsmall Cell
- What is being tested?
- SAF-189s
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 41 sitesChina
- Study dates
- 14 Nov 2016to 31 Mar 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
- Hemoglobin ≥ 90 g/L;
- Platelets (PLT) ≥ 100 × 109/L
- Serum total bilirubin ≤ 1.5 × ULN (if the patient has Gilbert's syndrome, ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN);
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- Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for patient with liver metastases);
- Creatinine clearance (CrCL) ≥ 50 mL/min (calculated by Cockcroft-Gault equation)
- 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);
Who cannot join
- 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;
- 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;
- Patients who received major surgery within 3 weeks before enrollment or have not adequately recovered from prior surgery;
- Patients with central nervous system (CNS) metastases requiring
- Clinical local intervention such as surgical excision, radiotherapy or other therapies
- 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).
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- 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:
- Repaglinide (cytochrome [CYP]2C8) and drugs metabolized via CYP3A4 enzyme within 1 week before enrollment;
- Medicines which are known to cause QT prolongation or torsade de pointes;
- Coumarin anticoagulants within 1 week before enrollment (low molecular weight heparin is permitted);
- 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.
Trial locations and contacts
41 sites in 1 country.
41 sites in 1 country
China41 sites, 41 recruiting
- Recruiting
Affiliated Hospital of Hebei University
Baoding, Hebei, 071000
Aimin Zang, Master, 13930881628, booszam@sina.com
Aimin Zang, Master
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100140
Li Zhang, Doctor, 13911339836, zhanglipumch@aliyun.com
Li Zhang, Doctor
- Recruiting
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100192
Ziping Wang, Doctor, 13301212676, wangzp2007@126.com
Ziping Wang, Doctor
- Recruiting
Beijing Chest Hospital,Capital Medical University
Beijing, Beijing Municipality, 101149
Zhe Liu, Doctor, 13651392121, liuzhe1968@aliyun.com
Zhe Liu, Doctor
- Recruiting
he First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004
Wei Li, Doctor, 13965282263, bbmcliwei@126.com
Wei Li, Doctor
- Recruiting
The First Hospital of Jilin University
Changchun, Jilin, 130031
Jiuwei Cui, Doctor, 15843073215, jdyycjw@163.com
Jiuwei Cui, Doctor
- Recruiting
Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
Changsha, Hunan, 410006
Nong Yang, Doctor, +86-0731-89762320, yangnong0217@163.com
Nong Yang, Doctor
- Recruiting
West China Hospital，Sichuan University
Chengdu, Sichuan, 610041
Ke Wang, Doctor, 18980602252, WangKeWK2019@126.com
Ke Wang, Doctor
- Recruiting
Guangdong Province People's General Hospital
Guangzhou, Guangdong, 510080
Jinji Yang, Doctor, +86-020-83827812, yangjinji2003@163.com
Yilong Wu, Doctor
- Recruiting
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Wangjun Liao, doctor, 13711448429, nfyyzlklwj@163.com
Wangjun Wangjun, doctor
- Recruiting
The First Affiliated Hospital, Medical School of Zhejiang University
Hangzhou, Zhejiang, 310009
Jianying Zhou, Doctor, +86-0571-87236877, drzjy@163.com
Jianying Zhou, Doctor
- Recruiting
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang, 310014
Liqin Lu, Bachelor, 13858039628, llq99@163.com
Liqin Lu, Bachelor
- Recruiting
SIR RUN RUN SHAW HOSPITAL Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Hongming Pan, Doctor, 13605716662, shonco@sina.cn
Hongming Pan, Doctor
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Yun Fan, Doctor, 13858182310, fanyun@zjcc.com
Yun Fan, Doctor
- Recruiting
Shulan (Hangzhou) Hospital
Hangzhou, Zhengjiang, 310000
Qiong Zhao, Doctor, 13588119268, jade1972@126.com
Qiong Zhao, Doctor
- Recruiting
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
GongYan Chen, Doctor, 13633668886, chengongyan@163.com
GongYan Chen, Dcotor
- Recruiting
Jieyang Peoples Hospital
Jieyang, Shanxi, 522000
Xiaofen Wang, Bachelor, 13542211822, 82395946@qq.com
Xiaofen Wang, Bachelor
- Recruiting
Jilin Cancer Hospital
Jilin City, Jilin, 130021
Ying Cheng, Bachelor, 0431-85871902, Jl.cheng@163.com
Ying Cheng, Bachelor
- Recruiting
Jinan Central Hospital
Jinan, Shandong, 250013
Yuping Sun, Doctor, 13370582181, sunypclinicaltrial@163.com
Yuping Sun, Doctor
- Recruiting
No. 960 Hospital of the Joint Service Support Force of Chinese People's Liberation Army
Jinan, Shandong, 250031
Baocheng Wang, Doctor, 13605310886, baochengwang960@sina.com
Baocheng Wang, Doctor
- Recruiting
Shandong Provincial Qianfoshan Hospital
Jinan, Shandong, 250061
Jun Wang, Doctor, 15806655997, ggjun2005@126.com
Jun Wang, Doctor
- Recruiting
Linyi Cancer Hospital
Linyi, Shandong, 276000
JianHua Shi, Master, 15963998868, shijianhualy@126.com
JianHua Shi, Master
- Recruiting
The second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Anwen Liu, Doctor, 13767120022, awliu666@163.com
Anwen Liu, Doctor
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 225001
Yongqian Shu, Doctor, 13951017570, shuyongqian@csco.org.cn
Yongqian Shu, Doctor
- Recruiting
The second peoples hospital of Neijiang
Neijiang, Sichuan, 641100
Ou Jiang, Doctor, 13990570757, jiangou816@163.com
Ou Jiang, Doctor
- Recruiting
Shanghai Chest Hospital,Shanghai Jiaotong University
Shanghai, Shanghai Municipality, 200030
Liyan Jiang, Doctor, 13916146759, jiang_liyan2000@126.com
Liyan Jiang, Doctor
- Recruiting
The first affiliated hospital of China medical university
Shenyang, Liaoning, 110001
Yunpeng Liu, Doctor, 13898865122, cmu_trial@163.com
Yunpeng Yunpeng, Doctor
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
Shenzhen, Guangdong, 518116
Shi Jin, Doctor, 18823361670, catherine-jinshi@163.com
Shi Shi, Doctor
- Recruiting
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050000
Cuimin Ding, Master, 13633083069, wjwdcm@sina.com
Cuimin Ding, Master
- Recruiting
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
Diansheng Zhong, Doctor, 13821377353, zhongdsh@hotmail.com
Diansheng Zhong, Doctor
- Recruiting
Tianjin Medical University Cancer Hospital
Tianjin, Tianjin Municipality, 300060
Changli Wang, Doctor, 13821086868, wangchangli309@163.com
Changli Wang, Doctor
- Not yet recruiting
Tianjin Peoples Hospital
Tianjin, Tianjin Municipality, 350000
Huaqing Wang, Doctor, 18622221223, huaqingw@163.com
Huaqing Wang, Doctor
- Recruiting
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Yuan Chen, Doctor, 18874052067, chenyuan008@163.com
Yuan Chen, Doctor
- Recruiting
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Xiaorong Dong, Doctor, 13986252286, hustwuhan@126.com
Xiaorong Dong, Doctor
- Recruiting
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Yanping Hu, Master, 13971385149, h-y-p@126.com
Yanping Hu, Master
- Recruiting
General Hospital of Xuzhou Mining Group
Xuzhou, Jiangsu, 221006
Baoqing Wang, Master, 13952234612, 13952234612@163.com
Baoqing Wang, Master
- Recruiting
Yanbian University Affiliated Hospital
Yanji, Jilin, 133000
Xionghu Shen, Doctor, 15526770368, xim918@126.com
Xionghu Shen, Doctor
- Recruiting
The Central Hospital of Yongzhou
Yongzhou, Hunan, 425006
Pengfei Luo, Master, 18608462505, 76756518@qq.com
Pengfei Luo, Master
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450014
Mingjun Li, Doctor, 13526502916, didilmj4505@sina.com
Mingjun Li, Doctor
- Recruiting
Zhengzhou Central Hospital
Zhengzhou, Henan, 450052
Shanyong Yi, Doctor, 15516991321, yisy2001@126.com
Shanyong Yi, Doctor
- Recruiting
The First Affiliated Hospital of Henan University of Science and Technology
Zhengzhou, Henan, 471003
Zhiye Zhang, Master, 13783100985, 13783100985@163.com
Zhiye Zhang, Master
About this study
Official title: 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.
Read the 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；
- Being tested
- SAF-189s
- Keywords
- ALK-rearranged, ALK-positive, ROS1-rearranged, ROS1-positive
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAF-189sDrug
Also called foritinib succinate
20mg，40mg，80mg，120mg，160mg，210mg，once daily
| Study group | Role | What they receive |
|---|---|---|
| SAF-189s | Experimental | 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. Receives: Drug: SAF-189s |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Dose Limiting Toxicity incidence within 24 days after the first dose in the dose escalation phase
Measured: 24 days after the first dose in the dose escalation phase
ORR
Objective response rate
Measured: until 6 months' treatment of the last patients in each cohort
Secondary outcomes (7)
TEAE
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.
Measured: through study completion, an average of 3 year
PFS
Progression-free survival (PFS)
Measured: 3 years
CBR
clinical benefit rate (CBR)
Measured: 3 years
DOR
duration of response (DoR)
Measured: 3 years
OS
Overall survival (OS)
Measured: 4 years
Cmax
Maximum Plasma Concentration
Measured: 1 years
CNS responses
Central nervous system efficacy evaluation，（time to CNS progression，CNS TTP），（CNS objective response rate，CNS ORR）,（duration of CNS response，CNS DOR）
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start14 Nov 2016
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yilong Wu, Doctor, Principal investigator, Guangdong Province People's General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04237805
- Sponsor's protocol ID
- SAF001
- Status last verified
- May 2021
- First submitted
- 15 Jan 2020
- Last updated
- 8 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang JJ, Zhou J, Liu SM, Li M, Zhang Z, Cheng Y, Fan Y, Pan H, Wang B, Chen G, Wang K, Jiang L, Hu Y, Shi J, Dong X, Ding C, Liu Y, Liu Z, Liao W, Li W, Wang J, Yi S, Zhao Q, Zang A, Chen Y, Cui J, Luo P, Shen X, Sun M, Wang C, Wu YL; SAF001 study group. Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study. Lancet Respir Med. 2024 Sep;12(9):671-680. doi: 10.1016/S2213-2600(24)00171-1. Epub 2024 Jul 23.
PubMed 39059398Xia ZJ, Ji YC, Sun DQ, Peng X, Gao YL, Fang YF, Zhao XD, Wang WB, Ding J, Geng MY, Ai J. SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors. Acta Pharmacol Sin. 2021 Jun;42(6):998-1004. doi: 10.1038/s41401-020-00513-3. Epub 2020 Sep 11.
PubMed 32918045
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04237805
- Acronym / sponsor ID
- SAF001
- Keywords
- ALK-rearranged, ALK-positive, ROS1-rearranged, ROS1-positive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 Nov 2016 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 23 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study comprises two phases: phase I dose escalation (including PK run-in period and treatment period) and phase II study.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SAF-189s | Experimental | Drug: SAF-189sThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
- Hemoglobin ≥ 90 g/L;
- Platelets (PLT) ≥ 100 × 109/L
Key exclusion criteria (12 listed)
- 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;
- 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;
- Patients who received major surgery within 3 weeks before enrollment or have not adequately recovered from prior surgery;
- Patients with central nervous system (CNS) metastases requiring
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAF-189sAlso: foritinib succinate20mg，40mg，80mg，120mg，160mg，210mg，once daily | Drug | SAF-189s |
Primary outcome
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
ORR
Time frame: until 6 months' treatment of the last patients in each cohort
Objective response rate
7 secondary outcomes
TEAE
Time frame: through study completion, an average of 3 year
PFS
Time frame: 3 years
CBR
Time frame: 3 years
DOR
Time frame: 3 years
OS
Time frame: 4 years
Cmax
Time frame: 1 years
CNS responses
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
- Derived from this study: PubMed 39059398Yang JJ, Zhou J, Liu SM, Li M, Zhang Z, Cheng Y, Fan Y, Pan H, Wang B, Chen G, Wang K, Jiang L, Hu Y, Shi J, Dong X, Ding C, Liu Y, Liu Z, Liao W, Li W, Wang J, Yi S, Zhao Q, Zang A, Chen Y, Cui J, Luo P, Shen X, Sun M, Wang C, Wu YL; SAF001 study group. Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study. Lancet Respir Med. 2024 Sep;12(9):671-680. doi: 10.1016/S2213-2600(24)00171-1. Epub 2024 Jul 23.
- Derived from this study: PubMed 32918045Xia ZJ, Ji YC, Sun DQ, Peng X, Gao YL, Fang YF, Zhao XD, Wang WB, Ding J, Geng MY, Ai J. SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors. Acta Pharmacol Sin. 2021 Jun;42(6):998-1004. doi: 10.1038/s41401-020-00513-3. Epub 2020 Sep 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yilong Wu, Doctor principal investigator
Guangdong Province People's General Hospital
41 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SAF-189s in people with Advanced Cancer and Advanced Solid Tumor, run by Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. at 41 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jinji Yang, Doctor (+86-020-83827812, yangjinji2003@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: 24 days after the first dose in the dose escalation phase). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04237805, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2021.