Phase I/II Study of SY-3505 in Patients With ALK-positive Advanced Non-small Cell Lung Cancer

NCT05257512 | Unknown Phase 1

• 1 other identifier: SY-3505-I
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/II, open-label and multi-center study of SY-3505, a third-generation ALK TKI, in patients with advanced ALK-positive non-small cell lung cancer (ALK-positive NSCLC).

Conditions

Non-small Cell Lung Cancer

Keywords

SY-3505; ALK; NSCLC

Outcome Measures

Primary Outcomes (3)

• Phase I: Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment

  Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) in Cycle 1.

  Dose-escalation Cycle 1 (each cycle is 28 days)

• Phase I: Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Characterization of the safety and tolerability

  Up to 24 months

• Phase II: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

  Anti-tumor activity of SY-3505

  Up to 24 months

Secondary Outcomes (11)

• Phase I: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

  Up to 24 months

• Phase I & II: Disease control rate (DCR) as assessed by RECIST 1.1 criteria

  Up to 24 months

• Phase I & II: Duration of response (DOR)

  Up to 24 months

• Phase I & II: Progression-free survival (PFS)

  Up to 24 months

• Phase I & II: Overall survival (OS)

  Up to 24 months

Study Arms (1)

Phase I/II Study of SY-3505

EXPERIMENTAL

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. In phase II, SY-3505 will be given at RP2D in advanced ALK-positive NSCLC patients.

Drug: SY-3505

Interventions

SY-3505 DRUG

The third-generation ALK TKI

Also known as: CT-3505

Phase I/II Study of SY-3505

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 18 years at the time of screening.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Estimated Life expectancy ≥ 12 weeks.
• 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.
• Dose-escalation phase: patients must have histological or cytological confirmed ALK-positive advanced NSCLC. Dose-expansion phase: patients must have histological or cytological confirmed ALK-positive advanced NSCLC and progressed after at least one prior line of ALK TKI therapy. Phase II: patients must have histological or cytological confirmed ALK-positive advanced NSCLC and progressed after only alectinib or ≥2 prior ALK TKIs treatment. 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.
• Patients without brain metastasis or with asymptomatic brain metastases (no need for intervention or stable more than 4 weeks after treated).
• 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.

You may not qualify if:

• 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.
• ECG evaluated QT interval corrected (Fridericia) (QTcF) of \> 450 msec in males or \> 470 msec in females or congenital long QT syndrome.
• Grade ≥ 3 peripheral neuropathy (CTCAE version 5.0).
• Any active autoimmune diseases or history of autoimmune diseases that require long-term steroid or other immunosuppressants treatment.
• 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.
• Patients being treated with any anticoagulants, prone to bleeding, or have a coagulation disorder.
• 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.
• Patient underwent major surgery within 4 weeks prior to starting trial treatment.
• 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.
• 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.
• 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).
• Patients with any active infection requiring systemic therapy within 4 weeks prior to starting trial treatment.
• 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.
• A clear previous history of neurological or psychiatric disorders, including dementia or diagnosed epilepsy for any reason.
• With a history (within 5 years) or presence of other malignancies, excluding cured skin basal cell carcinoma and carcinoma in situ of the cervix.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Related Publications (1)

• Shi Y, Hu X, Li X, Gong C, Wang K, Li Y, Zhang S, Luo Y, Wang P, Jiang L, Meng X, Dong X, Wang H, Yang R, Mei Q, Liu B, Yang L, Sun Y. Ficonalkib (SY-3505) in Advanced ALK-Positive NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 1/2 Study. J Thorac Oncol. 2024 Jun;19(6):898-911. doi: 10.1016/j.jtho.2024.01.015. Epub 2024 Jan 29.

  PMID: 38295954 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yinghui Sun, PhD

  Shouyao Holdings (Beijing) Co. LTD

  STUDY DIRECTOR

Central Study Contacts

Yinghui Sun, PhD

CONTACT

86-10-88858616; yhsun@centaurusbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: February 25, 2022
• Study Start: April 26, 2020
• Primary Completion: April 26, 2024
• Study Completion: August 26, 2024
• Last Updated: February 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)