A Study of SY-5933 in Patients With Advanced Solid Tumors Harboring the KRAS p.G12C Mutation

NCT06006793 | Unknown Phase 1

• 1 other identifier: SY-5933-I-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

KRAS p.G12C Mutation

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-limiting toxicities (DLTs)

  Number of participants with DLTs

  31 days after the first dose (single dose for 3 days and dose-escalation cycle 1 for 28 days)

• Number of participants with adverse events

  Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v5.0 criteria

  Up to 18 months

Secondary Outcomes (7)

• Pharmacokinetics (Cmax) for SY-5933

  Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)

• Pharmacokinetics (Tmax) for SY-5933

  Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)

• Pharmacokinetics (AUC0-t) for SY-5933

  Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)

• Pharmacokinetics (t½) for SY-5933

  Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)

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

  Up to 24 months

Study Arms (1)

Dose-escalation and Dose-expansion

EXPERIMENTAL

In dose-escalation phase, SY-5933 tablets will be administrated orally, repeat daily, 28 days as a dosing cycle, in ascending doses. In dose-expansion phase, RP2D of SY-5933 determined in dose-escalation phase will be administrated orally, repeat daily, 28 days as a dosing cycle.

Drug: SY-5933

Interventions

SY-5933 DRUG

KRAS p.G12C inhibitor

Also known as: SY-5933 tablet

Dose-escalation and Dose-expansion

Eligibility Criteria

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

You may qualify if:

• Men or women ≥ 18 years old
• Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
• Estimated life expectancy \>12 weeks.
• Patients must have at least one assessable lesion in the dose-escalation part and one measurable lesion in the dose-expansion part per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• In the dose-escalation part, patients must have histologically or cytologically confirmed advanced solid tumors harboring the KRAS p.G12C mutation and have progressed after standard therapy, or standard therapy is inappropriate or unavailable.
• In the dose-expansion part, patients must have histologically or cytologically confirmed advanced KRAS p.G12C mutant NSCLCs (cohort A) and CRCs, PDACs, and other solid tumors (Cohort B) and have progressed after standard therapy, or standard therapy is inappropriate or unavailable.
• Adequate organ function as defined in the below:
• Hepatic function Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times upper limit of normal (ULN), or ≤ 5 times ULN in the presence of liver metastases. Total serum bilirubin (TBIL) ≤ 1.5 times ULN; TBIL≤3×ULN and direct bilirubin（DBIL）≤1.5×ULN in the presence of liver metastases or with Gilbert's syndrome.
• Bone marrow function No blood transfusion or hematopoietic stimulator treatment within 7 days; absolute neutrophil count (ANC) ≥1.5×10\^9/L; platelets (PLT) count ≥75×10\^9/L; hemoglobin (Hb) ≥ 90 g/L.
• Renal function Creatinine clearance ≥ 50 mL/min. Coagulation function International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN.
• Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the first dose. Both male and female patients of reproductive potential must be willing to abstain completely 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.
• Willingness and ability to give informed consent and follow protocol procedures, and comply with follow-up visit requirements.

You may not qualify if:

• Dose-escalation phase: patients with known driver alterations other than KRAS p.G12C, e.g., EGFR, ALK, ROS1, RET, TRK, etc. (Enrollment of patients with co-mutations may be discussed with the investigator).
• Dose-expansion phase: prior use of selective KRAS inhibitors.
• Patients who received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, and other anti-tumor treatment within 3 weeks before the first administration, except for the following: Nitrosourea or mitomycin C was received within 6 weeks before the first administration; Oral fluoropyrimidines and small molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first administration; Chinese proprietary medicines with anti-tumor indications were received within 2 weeks before the first administration.
• Received other unapproved investigational drugs or treatments within 4 weeks prior to the first administration.
• Have undergone major organ surgery (excluding needle biopsy) or had significant trauma within 4 weeks prior to the first administration.
• Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≤ 1(exceptions for toxicities judged by the investigator to be of no safety concern, e.g. alopecia, grade 2 peripheral neurotoxicity, etc.).
• Presence of spinal cord compression, meningeal metastases, clinically symptomatic brain metastases, or need for increased steroid doses to control central nervous system (CNS) disease; patients with symptomatic CNS metastases that are already under control may be eligible for this study.
• Patients with active infection who need systematic anti-infective therapy within 2 weeks prior to the first administration.
• Active hepatitis (Hepatitis B: Hepatitis B virus surface antigen \[HBsAg\] positive with HBV DNA ≥2000 IU/mL; Hepatitis C: Hepatitis C virus antibody positive with HCV RNA ≥1000 IU/mL), HIV antibody positive, active syphilis (double positive for syphilis non-specific and syphilis specific antibodies) that is uncontrolled by treatment and inappropriate for enrollment as determined by the investigator.
• Presence of other lung diseases requiring systemic treatment or severe lung diseases such as active tuberculosis, interstitial lung disease, etc., which in the opinion of the investigator may affect the interpretation of the study results or place the patient at high risk;
• A history of serious cardiovascular and cerebrovascular disease, including but not limited to severe cardiac rhythm and conduction abnormalities, such as ventricular arrhythmias and degree II-III atrioventricular block requiring clinical intervention; Longer QT interval at rest (QTc \> 470 msec for women or \> 450 msec for men); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to first administration; Heart failure with the New York Heart Association (NYHA) Heart function rating ≥ II or left ventricular ejection fraction (LVEF) \< 50%; Clinically uncontrolled hypertension.
• Strong inhibitor or inducer of CYP3A, P-glycoprotein inducer or inhibitor used within 1 week or 5 half-lives (whichever is longer) prior to the first administration or expected to be used during the study period.
• Patients with malignancies other than tumors treated in this study (except malignancies that are cured and have not recurred within 2 years prior to study enrollment; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type).
• Severe gastrointestinal disease of clinical significance as determined by the investigator, including active ulcerative colitis, Crohn's disease, peptic ulcer disease, or previous surgical procedures that may have significantly affected drug absorption.
• History of allergy to study drug components or adjuvants.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, 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: August 10, 2023
• First Posted: August 23, 2023
• Study Start: August 10, 2023
• Primary Completion: February 15, 2025
• Study Completion: August 15, 2025
• Last Updated: September 1, 2023

Record last verified: 2023-08

Locations

CN (1)