Phase I/II Study of SY-5007, a RET Inhibitor, in Patients With RET-altered Advanced Solid Tumor

NCT05278364 | Unknown Phase 1

• 1 other identifier: SY-5007-I
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I/II, open-label, multi-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of SY-5007 administered orally to participants with advanced solid tumors, including RET Fusion-Positive NSCLC or RET-mutated MTC or other RET-altered advanced solid tumor.

Conditions

Non-Small Cell Lung Cancer; Medullary Thyroid Cancer; Solid Tumor

Keywords

SY-5007; RET-fusion positive NSCLC; RET-mutant MTC; RET-altered advanced solid tumor

Outcome Measures

Primary Outcomes (3)

• Phase I: Determine the dose-limiting toxicities (DLT) during the first 28-day cycle of SY-5007 treatment

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

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

• Phase I: Number of patients with adverse events and serious adverse events

  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-5007

  Up to 24 months

Secondary Outcomes (10)

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

Dose-escalation and Dose-expansion

EXPERIMENTAL

Dose-escalation Phase: Multiple doses of SY-5007 for oral administration. Dose Expansion Phase: RP2D of SY-5007 as determined during Dose Escalation.

Drug: SY-5007

Interventions

SY-5007 DRUG

a RET selective Inhibitor

Also known as: SY-5007 Capsule

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:

• For Phase I:
• Male or female, at least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Estimated life expectancy \>12 weeks.
• Patients must have at least one assessable lesion in dose-escalation part and one measurable lesion in dose-expansion part per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Dose-escalation Part: patients must have histological or cytological confirmed advanced solid tumours with RET alteration (fusion or mutation) and have progressed after standard therapy, or no standard or available curative therapy exists.
• Dose-expansion Part: Patients with advanced tumor must have histological or cytological confirmed RET alteration, including NSCLC patients with RET-fusion or MTC patients with RET-mutation or other patients with RET alteration, and either have progressed after standard therapy or no standard/ available curative therapy exists.
• Patients must have adequate organ function as defined in the below:
• Hepatic function:
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN) if no hepatic metastases are present, or otherwise ≤ 5 times ULN, Total serum bilirubin (TBIL) ≤ 1.5 times ULN.
• Bone marrow function (No blood transfusion or haematopoietic stimulating factor treatment within 10 days prior to testing):
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L; Platelets (PLT) count ≥ 75 x 10⁹/L; Hemoglobin (Hb) ≥ 85 g/L.
• Renal function:
• Creatinine clearance ≥ 50 mL/min.
• Coagulation function:

You may not qualify if:

• Dose-expansion Part: Patient's cancer has a known primary driver alteration other than RET. e.g. EGFR, ALK, ROS1, KRAS, etc.
• Dose-expansion Part: Patients previously treated with a selective RET inhibitor.
• Patients received systemic antitumor therapy, including chemotherapy, radiotherapy, biologic therapy, endocrine therapy, or immunotherapy within 3 weeks prior to the first dose, except for the following:
• Nitrosoureas or mitomycin C within 6 weeks; Oral fluorouracils and small molecule drugs within 2 weeks or within 5 half-life periods of the drug (whichever is longer); Antitumour traditional Chinese medicine within 2 weeks.
• Patients received other unlisted clinical trial drugs or treatments within 4 weeks prior to the first dose.
• Patients underwent major organ surgery (excluding puncture biopsy) or had significant trauma within 4 weeks prior to the first dose.
• Adverse effects of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade rating of ≤ grade 1 (except for toxicity judged by the investigator be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.)
• Patients have symptomatic central nervous system (CNS) metastases, meningeal metastases, or a primary CNS tumor that is associated with progressive neurological symptoms.
• Patients with active uncontrolled systemic bacterial, viral, or fungal infection despite optimal treatment (chronic disease screening not required).
• 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.
• Patients have a history of severe cardiovascular disease, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities, e.g. ventricular arrhythmia requiring clinical intervention, II-III degree atrioventricular block, etc.
• Mean QT interval corrected using Fridericia's formula (QTcF)\> 480ms at rest. Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke or other grade 3 or higher cardiovascular or cerebrovascular events within 6 months prior to the first dose.
• New York Heart Association (NYHA) ≥ class II heart failure or left ventricular ejection fraction (LVEF) \< 50%.
• Hypertension remains uncontrolled after aggressive antihypertensive therapy.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (2)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Tianjin People's Hospital

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

Related Publications (1)

• Li W, Wang Y, Xiong A, Gao G, Song Z, Zhang Y, Huang D, Ye F, Wang Q, Li Z, Liu J, Xu C, Sun Y, Liu X, Zhou F, Zhou C. First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors. Signal Transduct Target Ther. 2024 Nov 4;9(1):300. doi: 10.1038/s41392-024-02006-9.

  PMID: 39489747 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Medullary

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

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: March 8, 2022
• First Posted: March 14, 2022
• Study Start: April 23, 2021
• Primary Completion: January 1, 2025
• Study Completion: February 10, 2025
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (2)