Trial Title:
A Study of SY-5933 in Patients With Advanced Solid Tumors Harboring the KRAS p.G12C Mutation
NCT ID:
NCT06006793
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
KRAS p.G12C Mutation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SY-5933
Description:
KRAS p.G12C inhibitor
Arm group label:
Dose-escalation and Dose-expansion
Other name:
SY-5933 tablet
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.
Detailed description:
The study will be conducted in 2 parts: Part 1 - Dose Escalation and Part 2 - Dose
Expansion. Part 1 is aimed at evaluating the safety, tolerability, PK and
pharmacodynamics of SY-5933 and determining the recommended phase II dose (RP2D) of
repeat daily (QD) dosing schedule in subjects with advanced KRAS p.G12C mutant solid
tumors using accelerated titration and 3+3 design. The dose escalation part of the study
will consist of 7-13 subjects and the dose expansion part will consist of 30-60
additional subjects, comprising 2 cohorts. Cohort A includes patients with non-small cell
lung cancer (NSCLC) harboring KRAS p.G12C mutations and Cohort B includes patients with
other advanced solid tumors (colorectal, pancreatic cancers, etc.). Patients in dose
expansion study will receive SY-5933 tablets QD, oral administration, 28 days as a dosing
cycle, to further evaluate the safety, PK profile, and efficacy of SY-5933, and to
further define RP2D. Administration of SY-5933 may continue until evidence of disease
progression, intolerance to SY-5933, or withdrawal of consent.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men or women ≥ 18 years old
2. Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
3. Estimated life expectancy >12 weeks.
4. 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.
5. 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.
6. 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.
7. 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.
8. Willingness and ability to give informed consent and follow protocol procedures, and
comply with follow-up visit requirements.
Exclusion Criteria:
1. 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).
2. Dose-expansion phase: prior use of selective KRAS inhibitors.
3. 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.
4. Received other unapproved investigational drugs or treatments within 4 weeks prior
to the first administration.
5. Have undergone major organ surgery (excluding needle biopsy) or had significant
trauma within 4 weeks prior to the first administration.
6. 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.).
7. 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.
8. Patients with active infection who need systematic anti-infective therapy within 2
weeks prior to the first administration.
9. 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.
10. 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;
11. 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.
12. 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.
13. 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).
14. 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.
15. History of allergy to study drug components or adjuvants.
16. Pleural, abdominal, or pericardial effusions that are poorly controlled despite
intervention (defined as effusion that has grown significantly within 2 weeks of
removal and is symptomatic requiring re-puncture or other intervention).
17. Uncontrolled diabetes mellitus [fasting blood glucose ≥10 mmol/L and/or glycated
hemoglobin (HbA1c) ≥8%], uncontrolled symptomatic hyperthyroidism or hypothyroidism,
uncontrolled symptomatic hypercalcemia or hypocalcemia.
18. Have a coagulation disorder or bleeding tendency, including an arterial or venous
thromboembolic event or any life-threatening bleeding event within 6 months prior to
first administration, or have a lesion involving a major blood vessel, or have a
bleeding tendency as determined by the investigator.
19. Pregnant or lactating women.
20. Presence of any condition that may increase the risks associated with the
administration of the study drug or that may affect the interpretation of the study
results, or poor patient compliance, or any other condition that, in the opinion of
the investigator, makes the enrollment inappropriate.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Caicun Zhou, PhD
Phone:
13301825532
Email:
caicunzhoudr@163.com
Start date:
August 10, 2023
Completion date:
August 15, 2025
Lead sponsor:
Agency:
Shouyao Holdings (Beijing) Co. LTD
Agency class:
Other
Source:
Shouyao Holdings (Beijing) Co. LTD
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06006793
