Brief Title
A Dose-Escalation/ Dose-Expansion Study of SY-3505 in Patients With ALK-positive Non-small Cell Lung Cancer
Official Title
A Phase I, Open-Label, Multi-Center, Dose-escalation/ Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SY-3505 Capsule in Patients With ALK-positive Non-small Cell Lung Cancer
Brief Summary
This is a Phase 1, open-label and multi-center study of SY-3505, a third-generation ALK TKI,
in patients with ALK-positive non-small cell lung cancer (ALK-positive NSCLC). This study has
two phases: dose-escalation phase and dose-expansion phase.
Detailed Description
Dose-escalation study phase is designed to determine the dose-limiting toxicity (DLT)
according to a 3+3 design and recommended phase II dose (RP2D) and to characterize the
safety, tolerability, and pharmacokinetics (PK) profile of SY-3505. Other dose regimens may
be explored based on the analysis of emerging PK and safety data. At this study phase,
SY-3505 administered orally once daily (QD) in 28-day treatment cycles to adult patients with
ALK-positive NSCLC),
Dose-expansion study phase is designed to evaluate the antitumor activity (ORR and DOR) of
SY-3505 in patients with ALK-positive NSCLC.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment
Secondary Outcome
Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria
Condition
Non-small Cell Lung Cancer
Intervention
SY-3505
Study Arms / Comparison Groups
Dose-escalation and Dose-expansion
Description: SY-3505 will be given orally in ascending doses (escalation cohort), until the DLT or RP2D is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
70
Start Date
April 26, 2020
Completion Date
December 30, 2022
Primary Completion Date
June 30, 2022
Eligibility Criteria
Inclusion Criteria:
1. Male or female, age ≥ 18 years at the time of screening.
2. Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
3. Estimated Life expectancy ≥ 12 weeks.
4. Must have either at least one measurable lesion with no prior local treatment or
measurable lesions with definite progression (Bone metastases alone were not accepted)
after local treatment per Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1.
5. Escalation Part: Patients must have histological or cytological confirmed ALK-positive
advanced non-small cell lung cancer. Expansion Part: patients must have histological
or cytological confirmed ALK-positive advanced non-small cell lung cancer and
progressed after 1 to 2 prior lines of ALK inhibitor therapy. The pathological report
requires either positivity for ALK gene expression determined by fluorescence in-situ
hybridization (FISH) assay, immunohistochemistry (IHC), reverse
transcription-polymerase chain reaction (RT-PCR), next-generation sequencing (NGS) or
other identified methods from previous reports and provide tissue for ALK retest if
possible or providing tissue for ALK test if no previous report is available.
6. Patients without brain metastasis or with asymptomatic brain metastases (no need for
intervention or stable more than 4 weeks after treated).
7. Adequate organ function within 10 days prior to the study of treatment as defined in
the below:
Hepatic function
Total serum bilirubin (TBIL) ≤ 1.5 times upper limit of normal (ULN); Aspartate
transaminase (AST), alanine transaminase (ALT) and γ- glutamyltransferase (GGT) ≤ 2.5
times ULN if no demonstrable liver metastases, or otherwise ≤ 5 times ULN.
Bone marrow function
Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L; Platelets (PLT) count ≥ 100 x 10⁹/L;
Hemoglobin (Hb) ≥ 90 g/L.
Renal function
Creatinine clearance ≥ 60 mL/min.
Pancreatic function
Serum total amylase ≤1.5 times ULN; Serum lipase ≤ 1.5 times ULN.
Blood glucose
Fasting Blood Glucose (FBG) ≤ 200 mg/dL (11.1 mmol/L).
Serum lipid
Serum cholesterol ≤ 500 mg/dL (12.92 mmol/L).
Cardiac function
Left ventricular ejection fraction (LVEF) ≥ 50%.
8. Any toxicity of previous antineoplastic treatments was restored to ≤ 1 (except hair
loss).
9. Female patients with reproductive potential must have a negative serum pregnancy test,
male and female patients of childbearing potential must be willing to completely
abstain or agree to use an appropriate method of contraception during the entire study
duration and for at least 3 months after the last dose of study medication.
10. Willingness and ability to give informed consent and follow protocol procedures, and
comply with follow-up visit requirements.
Exclusion Criteria:
1. Any of the following within 6 months prior to starting trial treatment:
Cerebrovascular accident/ stroke, myocardial infarction, severe/ unstable angina,
congestive heart failure (New York Heart Association Classification Class ≥II),
second- or third- degree atrioventricular (AV) block (unless paced) or any AV block
with PR interval >220 msec, or any grade of uncontrolled atrial fibrillation.
2. ECG evaluated QT interval corrected (Fridericia) (QTcF) of > 450 msec in males or >
470 msec in females or congenital long QT syndrome.
3. Grade ≥ 3 peripheral neuropathy (CTCAE version 5.0).
4. Any active autoimmune diseases or history of autoimmune diseases that require
long-term steroid or other immunosuppressants treatment.
5. Previous medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis which required steroid treatment, or any evidence of
clinically active interstitial lung disease.
6. Patients being treated with any anticoagulants, prone to bleeding, or have a
coagulation disorder.
7. Active hepatitis (Hepatitis B: HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL; Hepatitis B:
HCV antibody-positive and HCV-RNA ≥ 1000 IU/ml), HIV antibody-positive; Active
syphilis.
8. Patient underwent major surgery within 4 weeks prior to starting trial treatment.
9. Patients received radical radiotherapy within 4 weeks, palliative radiotherapy within
2 weeks, or radioactive agents (strontium, samarium, etc.) within 8 weeks prior to
starting trial treatment.
10. Patients received systemic antitumor therapy, including chemotherapy, immunotherapy,
biotherapy (cancer vaccine, cytokine or cancer growth control factor), or clearly
indicated antitumor traditional Chinese medicine within 4 weeks (targeted therapy
within 2 weeks) prior to starting trial treatment.
11. Patients treated with the following drugs and could not be discontinued at least 7
days prior to starting trial treatment and during the entire study duration: drugs
known to be strong inducers or suppressors of CYP3A (for details, see prohibited
combination drugs in this trial).
12. Patients with any active infection requiring systemic therapy within 4 weeks prior to
starting trial treatment.
13. Comorbidities that may seriously endanger the patient's safety or affect the
completion of the trial, such as severe diabetes, according to the judgment of
investigator.
14. A clear previous history of neurological or psychiatric disorders, including dementia
or diagnosed epilepsy for any reason.
15. With a history (within 5 years) or presence of other malignancies, excluding cured
skin basal cell carcinoma and carcinoma in situ of the cervix.
16. Other situations that may increase the risks related to the study medication,
interfere with the interpretation of the study results, affect compliance of the
trial, etc. are determined by the investigator to be not suitable for the trial.
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Yinghui Sun, PhD, 86-10-88858616, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT05257512
Organization ID
SY-3505-I
Responsible Party
Sponsor
Study Sponsor
Shouyao Holdings (Beijing) Co. LTD
Study Sponsor
Yinghui Sun, PhD, Study Director, Shouyao Holdings (Beijing) Co. LTD
Verification Date
February 2022