A Dose-Escalation/ Dose-Expansion Study of SY-3505 in Patients With ALK-positive Non-small Cell Lung Cancer

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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


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


Non-small Cell Lung Cancer



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.


* 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


Estimated Enrollment


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

          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

          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

         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.




18 Years - 75 Years

Accepts Healthy Volunteers



Yinghui Sun, PhD, 86-10-88858616, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Shouyao Holdings (Beijing) Co. LTD

Study Sponsor

Yinghui Sun, PhD, Study Director, Shouyao Holdings (Beijing) Co. LTD

Verification Date

February 2022