Advanced Solid TumorPhase 1NCT06006793
A Study of SY-5933 in Patients With Advanced Solid Tumors Harboring the KRAS p.G12C Mutation
A Phase 1 study testing SY-5933 in people with Advanced Solid Tumor, run by Shouyao Holdings (Beijing) Co. LTD at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- SY-5933
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 10 Aug 2023to 15 Aug 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.).
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- 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.
- 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).
- 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.
- 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.
- Pregnant or lactating women.
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Pulmonary Hospital
Shanghai
Caicun Zhou, PhD, 13301825532, caicunzhoudr@163.com
About this study
Official title: A Phase I, Dose-escalation/Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of SY-5933 Tablets in Patients With Advanced KRAS p.G12C Mutant Solid Tumors
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.
Read the 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.
- Conditions
- Advanced Solid Tumor
- Being tested
- SY-5933
- Keywords
- KRAS p.G12C Mutation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SY-5933Drug
Also called SY-5933 tablet
KRAS p.G12C inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: SY-5933 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose-limiting toxicities (DLTs)
Number of participants with DLTs
Measured: 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
Measured: Up to 18 months
Secondary outcomes (7)
Pharmacokinetics (Cmax) for SY-5933
Defined as maximum observed plasma concentration
Measured: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
Pharmacokinetics (Tmax) for SY-5933
Defined as time to maximum plasma concentration
Measured: 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
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
Measured: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
Pharmacokinetics (t½) for SY-5933
Defined as the apparent plasma terminal phase disposition half-life
Measured: 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
Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
Measured: Up to 24 months
Disease control rate (DCR) as assessed by RECIST 1.1 criteria
Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
Measured: Up to 24 months
Duration of response (DOR)
Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start10 Aug 2023
- Primary completion15 Feb 2025 (estimated)
- Study completion15 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yinghui Sun, PhD, Study director, Shouyao Holdings (Beijing) Co. LTD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06006793
- Sponsor's protocol ID
- SY-5933-I-01
- Status last verified
- Aug 2023
- First submitted
- 10 Aug 2023
- Last updated
- 1 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-escalation/Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of SY-5933 Tablets in Patients With Advanced KRAS p.G12C Mutant Solid Tumors
- ClinicalTrials.gov ID
- NCT06006793
- Acronym / sponsor ID
- SY-5933-I-01
- Conditions
- Advanced Solid Tumor
- Keywords
- KRAS p.G12C Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTDUniversity, hospital or other
- Study start
- 10 Aug 2023 (actual)
- Primary completion
- 15 Feb 2025 (estimated)
- Study completion
- 15 Aug 2025 (estimated)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation and Dose-expansion | Experimental | Drug: SY-5933In 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SY-5933Also: SY-5933 tabletKRAS p.G12C inhibitor | Drug | Dose-escalation and Dose-expansion |
Primary outcome
Incidence of Dose-limiting toxicities (DLTs)
Time frame: 31 days after the first dose (single dose for 3 days and dose-escalation cycle 1 for 28 days)
Number of participants with DLTs
Number of participants with adverse events
Time frame: Up to 18 months
Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v5.0 criteria
7 secondary outcomes
Pharmacokinetics (Cmax) for SY-5933
Time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
Pharmacokinetics (Tmax) for SY-5933
Time frame: 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
Time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
Pharmacokinetics (t½) for SY-5933
Time frame: 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
Time frame: Up to 24 months
Disease control rate (DCR) as assessed by RECIST 1.1 criteria
Time frame: Up to 24 months
Duration of response (DOR)
Time frame: Up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yinghui Sun, PhD study director
Shouyao Holdings (Beijing) Co. LTD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SY-5933 in people with Advanced Solid Tumor, run by Shouyao Holdings (Beijing) Co. LTD at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yinghui Sun, PhD (86-10-88858616, yhsun@centaurusbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose-limiting toxicities (DLTs) (time frame: 31 days after the first dose (single dose for 3 days and dose-escalation cycle 1 for 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.