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

  • STATUS
    Recruiting
  • End date
    Mar 31, 2026
  • participants needed
    280
  • sponsor
    Shanghai Fosun Pharmaceutical Development Co, Ltd.
Updated on 24 February 2022
cancer
systemic therapy
measurable disease
lung cancer
serum bilirubin
kinase inhibitor
metastasis
neutrophil count
liver metastasis
ROS1
cancer treatment
cancer chemotherapy
alopecia
crizotinib
lung carcinoma
secondary malignant neoplasm of liver
proto-oncogene tyrosine-protein kinase ros

Summary

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

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 : cohort1ROS1-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

Details
Condition Advanced Cancer, Advanced Solid Tumor, Lung Cancer, Nonsmall Cell
Treatment SAF-189, SAF-189s
Clinical Study IdentifierNCT04237805
SponsorShanghai Fosun Pharmaceutical Development Co, Ltd.
Last Modified on24 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Have a full understanding of this study and voluntarily sign an informed consent form (ICF) 2Phase 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 : cohort1ROS1-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
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
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; 9Within 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)
Serum total bilirubin 1.5 ULN (if the patient has Gilbert's syndrome, 3 ULN and direct bilirubin 1.5 ULN)
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)

Exclusion Criteria

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
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); 6Difficulty 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) 7Patients who are taking the following medicines
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)
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; 14Any 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; 15Spinal cord metastases with potential risk or symptoms of spinal cord compression 16The second cohort received ROS1 inhibitors other than crizotinib 17The patient had uncontrollable amounts of pleural effusion, ascites, and pericardial effusion
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
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