A Study of SY-3505 in Patients With Advanced LTK Fusion-Positive Solid Tumors

NCT06037317 | Recruiting Phase 1

• 1 other identifier: CT-3505-I-03
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, multicenter, phase Ib study to evaluate the efficacy and safety of SY-3505 capsule in patients with locally advanced or metastatic, LTK fusion-positive solid tumor who have progressed on or are intolerant to prior standard therapy.

Conditions

Advanced Solid Tumor

Keywords

SY-3505; Leukocyte receptor tyrosine kinase fusion-positive

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Characterization of the safety and tolerability

  Up to 2 years

• Incidence of dose limiting toxicities (DLTs)

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

  Escalation Cycle 1 (28 days)

Secondary Outcomes (7)

• Pharmacokinetics (Cmax) for SY-3505

  Protocol-defined time points during Cycle 1 and 2 of treatment (each cycle is 28 days)

• Pharmacokinetics (Tmax) for SY-3505

  Protocol-defined time points during Cycle 1 and 2 of treatment (each cycle is 28 days)

• Pharmacokinetics (AUC0-t) for SY-3505

  Protocol-defined time points during Cycle 1 and 2 of treatment (each cycle is 28 days)

• Pharmacokinetics (t½) for SY-3505

  Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days)

• Overall Response Rate (ORR) as assessed by RECIST v1.1

  Up to 2 years

Study Arms (1)

Dose-escalation and Dose-expansion

EXPERIMENTAL

In dose-escalation phase, SY-3505 will be given orally in ascending doses (escalation cohort) until the DLT or RP2D is reached. In dose-expansion phase, SY-3505 will be given at RP2D in 28-day cycle continuously.

Drug: SY-3505

Interventions

SY-3505 DRUG

LTK tyrosine kinase inhibitor

Also known as: CT-3505, Ficonalkib

Dose-escalation and Dose-expansion

Eligibility Criteria

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

You may qualify if:

• Patients must meet all of the following criteria to be eligible for this study:
• Age ≥ 18 years at the time of signing the Informed Consent Form (ICF).
• Histologically or cytologically confirmed locally advanced (as assessed by the investigator, unresectable tumor or tumor recurrence following standard therapy with evidence of progression \[PD\] or intolerance to prior therapy) or metastatic solid tumor and failure of standard treatment with evidence of disease progression on imaging.
• Agreement to provide a required tumor tissue sample (preferably fresh biopsy tissue or archived tumor tissue within 2 years prior to first dosing) that has been tested by the central laboratory and determined to be positive for LTK gene fusion.
• At least one measurable extracranial lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Expected survival of ≥ 3 months.
• Resolution of any treatment-related AEs related to prior anticancer therapy to NCI-CTCAE v 5.0 grade ≤ 1 (excluding toxicities judged by the investigator to be of no safety concern, e.g., hair loss, prior platinum-related grade 2 peripheral neuropathy) before the first dosing.
• Organ function levels must meet the following requirements:
• No blood products, hematopoietic growth factors (e.g., G-CSF, erythropoietin), or other drugs that correct abnormal blood counts for at least 2 weeks before first dosing and the following blood counts: ANC ≥ 1.5 × 10\^9/L, PLT count ≥ 100 × 10\^9/L, Hb ≥ 90 g/L.
• Liver function: TBIL ≤ 1.5 × upper limit of normal (ULN) in the absence of liver metastases, and AST and ALT ≤ 2.5 × ULN; in the presence of liver metastases, AST and ALT ≤ 5.0 × ULN, and TBIL ≤ 3 × ULN.
• Pancreatic function: Serum total amylase ≤ 1.5 × ULN and serum lipase ≤ 1.5 × ULN (subjects with serum total amylase \> 1.5 × ULN but with serum lipase within the ULN range may be eligible).
• Renal function: Creatinine clearance (Ccr) ≥ 50 mL/min (calculated using the Cockcroft and Gault formula).
• Coagulation function: International normalized ratio (INR) and prothrombin time (PT) ≤ 2 × ULN (except for patients receiving anticoagulant therapy).
• Able to take oral medications and comply with scheduled visits and related procedures per protocol.

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for this study:
• Carrying known major driver gene mutations other than LTK gene, such as EGFR, MET, ALK, ROS1, NTRK, etc. (Patients with co-mutations may be discussed with the investigator for eligibility).
• History of hypersensitivity reactions to any component or excipient of SY-3505 capsules.
• Concurrent primary malignancy, with the following exceptions: adequately treated in situ carcinoma, non-melanoma skin cancer, in situ cervical cancer, or in situ breast cancer, and cured malignancies without recurrence for at least 2 years prior to study entry.
• Symptomatic primary central nervous system (CNS) tumors, symptomatic CNS metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Patients with stable CNS disease (defined as no evidence of progression on imaging for at least 4 weeks prior to first dosing, with all neurological symptoms returned to baseline, and without evidence of new or enlarging brain metastases, and no CNS surgery or radiation treatment within 4 weeks prior to first dosing, and no stereotactic radiosurgery \[SRS\] within 2 weeks prior to first dosing, and no steroids for at least 2 weeks) are eligible. (Note: Carcinomatous meningitis is not allowed, regardless of clinical stability).
• Presence of any of the following conditions or diseases at screening that are inadequately controlled with the best possible medical management:
• Active systemic bacterial, viral, or fungal infections.
• Pleural effusion, peritoneal effusion, or pericardial effusion that is not controlled after intervention (defined as significant if reaccumulation of fluid requiring drainage occurs within 2 weeks of the prior intervention with associated symptoms).
• Poorly controlled diabetes mellitus (defined as fasting blood glucose ≥ 11.1 mmol/L and/or HbA1c ≥ 8%).
• Symptomatic hyperthyroidism or hypothyroidism not well controlled by medical management as assessed by the investigator.
• Clinically significant electrolyte disturbances (e.g., severe hypocalcemia, hypomagnesemia, hypokalemia) as assessed by the investigator.
• Clinically significant gastrointestinal diseases that may interfere with the absorption of study drug (e.g., active ulcerative colitis, Crohn's disease, gastrointestinal ulcers, or major gastrointestinal surgery that might affect drug absorption).
• Severe cardiovascular diseases/abnormalities meeting any of the following criteria:
• QT interval corrected for heart rate (QTcF) \> 470 msec for females or \> 450 msec for males as calculated by the Fridericia formula during screening (subjects with suspected drug-induced QTcF prolongation that is assessed by the investigator as safely controllable may be eligible after correction with medication).
• Left ventricular ejection fraction (LVEF) \< 50%.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

RECRUITING

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: September 7, 2023
• First Posted: September 14, 2023
• Study Start: May 30, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): May 30, 2026
• Last Updated: February 2, 2024

Record last verified: 2023-06

Locations

CN (1)