Study of SY-5933 Plus CT-707 in Advanced Solid Tumors With KRAS p.G12C Mutation

NCT06970132 | Not Yet Recruiting Phase 1

• 1 other identifier: SY-5933-II-01
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase Ib/II, open-label, single-arm study evaluates the safety, tolerability, pharmacokinetics, and preliminary efficacy of SY-5933 tablets combined with CT-707 tablets in patients with advanced solid tumors harboring the KRAS p.G12C mutation. The Phase Ib includes a dose-escalation phase to determine the optimal dosing regimen based on safety and pharmacokinetic data. In Phase II, four cohorts will be enrolled: advanced KRAS p.G12C mutated non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors.

Conditions

Advanced Solid Tumor

Keywords

KRAS p.G12C Mutation

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) in KRAS p.G12C Mutant Advanced Solid Tumors in Phase Ib

  Evaluate the safety and tolerability of SY-5933 combined with CT-707

  Up to 24 months

• Dose-limiting toxicity (DLT) of SY-5933 combined with CT-707 in KRAS p.G12C Mutant Advanced Solid Tumors in Phase Ib

  To determine the recommended phase 2 dose (RP2D)

  From first dose to end of DLT observation period (approximately 28 days)

• Objective response rate (ORR) of SY-5933 combined with CT-707 in KRAS p.G12C Mutant Advanced Solid Tumors in Phase II

  Evaluate the ORR based on RECIST v1.1 criteria to assess the preliminary efficacy of SY-5933 combined with CT-707 in patients with advanced solid tumors harboring KRAS p.G12C mutation

  Up to 24 months

Secondary Outcomes (9)

• Pharmacokinetics (Cmax)

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

• Pharmacokinetics (Tmax)

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

• Pharmacokinetics (AUC0-t)

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

• Pharmacokinetics (t½)

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

• ORR of SY-5933 combined with CT-707 in KRAS p.G12C mutant advanced solid tumors in Phase Ib

  Up to 24 months

Other Outcomes (4)

• Effect of SY-5933 combined with CT-707 on QT Interval Corrected by Fridericia (QTcF)

  Up to 24 months

• Baseline tumor FAK protein expression intensity

  Up to 24 months

• Plasma phospho-FAK (Tyr397) levels

  Up to 24 months

Study Arms (1)

Phase Ib/II study of SY-5933 and CT-707 combination

EXPERIMENTAL

In Phase Ib, six KRAS p.G12C mutation-positive patients will first receive 800 mg QD SY-5933 and 600 mg QD CT-707 for dose escalation. The dose of CT-707 may be adjusted based on safety, pharmacokinetic and efficacy data. 1-2 regimens will be selected for an expansion phase. The Phase II study will treat KRAS p.G12C mutation-positive patients with SY-5933 and CT-707 across four tumor types (NSCLC, colorectal cancer, pancreatic cancer, and other solid tumors) until disease progression or intolerable toxicity.

Drug: SY-5933; Drug: CT-707

Interventions

SY-5933 DRUG

KRAS p.G12C inhibitor

Also known as: SY-5933 tablet

Phase Ib/II study of SY-5933 and CT-707 combination

CT-707 DRUG

Focal Adhesion Kinase (FAK) inhibitor

Also known as: CT-707 tablet, SY-707 tablet, Conteltinib

Phase Ib/II study of SY-5933 and CT-707 combination

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria to be eligible for enrollment in this study:
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor.
• Age ≥ 18 years at the time of informed consent, regardless of gender.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Presence of at least one extracranial target lesion (as defined by RECIST v1.1). Lesions previously treated with radiation therapy may only be considered target lesions if there is clear progression following radiation therapy.
• KRAS (G12C) mutation positive. For the Phase Ib dose-escalation phase, participants must have previously undergone standard treatment for advanced tumors. In the Phase II cohorts: Cohort 1 (NSCLC), Cohort 2 (colorectal cancer), Cohort 3 (pancreatic cancer), and Cohort 4 (other solid tumors). In the Phase Ib expansion phase, except for NSCLC, patients with other tumor types must have previously undergone standard treatment for advanced tumors. For Cohort 2-4 of Phase II, initial enrollment will prioritize patients who have received prior standard treatment, but frontline patients may be considered if sufficient efficacy and safety data are collected during Phase Ib or the Phase II study, following review by the Safety Monitoring Committee (SMC) to assess the benefit-risk ratio.
• Adequate organ function as defined below:
• Liver function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× upper limit of normal (ULN), or ≤ 5× ULN if liver metastasis is present.
• Total bilirubin (TBIL) ≤ 1.5× ULN, or ≤ 3× ULN and direct bilirubin (DBIL) ≤ 1.5× ULN if liver metastasis or Gilbert's syndrome is present.
• Bone marrow function (No blood products, hematopoietic growth factors, or other treatments for hematological abnormalities within 7 days prior to dosing):
• Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L. Platelet count (PLT) ≥ 75×10\^9/L. Hemoglobin (Hb) ≥ 90 g/L.
• Renal function:
• Creatinine clearance ≥ 50 mL/min.

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from this study:
• For patients in the Ib expansion cohort and Phase II, the presence of known major oncogenic driver alterations other than KRAS G12C mutation, such as EGFR, ALK, ROS1, RET, NTRK, KRAS G12D, etc. (Patients with co-mutations may be considered for enrollment after discussion with the investigator).
• Prior treatment with a KRAS p.G12C inhibitor.
• Receipt of chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, or other anti-tumor therapies within 3 weeks prior to the first dose of study drug, except for the following:
• Nitrosoureas or mitomycin C administered within 6 weeks prior to the first dose;
• Oral fluoropyrimidines and small molecule targeted agents administered within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose.
• Receipt of any investigational agents or therapies not yet approved for marketing within 4 weeks prior to the first dose.
• Underwent major surgery involving major organs (excluding needle biopsy) or experienced significant trauma within 4 weeks prior to the first dose.
• Adverse events from prior anti-cancer therapies have not recovered to Grade ≤1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 (except for toxicities assessed by the investigator as posing no safety risk, such as alopecia and Grade 2 peripheral neuropathy).
• Presence of spinal cord compression, leptomeningeal metastasis, symptomatic brain metastases, or CNS disease requiring escalating doses of corticosteroids. Subjects with previously treated and stable CNS metastases are eligible if neurologic function is stable, no new neurologic deficits are observed on clinical examination, and there is no evidence of radiographic progression for at least 4 weeks prior to the first dose. If corticosteroids are required for CNS metastases, the dose must have been stable for at least 2 weeks prior to study entry.
• Active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose.
• Active hepatitis infection (defined as HBsAg positive with HBV-DNA ≥2000 IU/mL; or HCV antibody positive with HCV-RNA ≥1000 IU/mL), HIV infection, or active syphilis (both non-treponemal and treponemal tests positive) that remains uncontrolled despite appropriate treatment, as assessed by the investigator.
• Presence of other severe pulmonary conditions requiring systemic treatment, such as active tuberculosis, interstitial lung disease, etc., that may, in the opinion of the investigator, affect study results or place the subject at unacceptable risk.
• History or presence of severe cardiovascular or cerebrovascular diseases/abnormalities, including but not limited to:
• Significant arrhythmias or conduction abnormalities requiring clinical intervention (e.g., clinically significant ventricular arrhythmias, Grade II-III atrioventricular block);

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

MeSH Terms

Interventions

conteltinib

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: April 27, 2025
• First Posted: May 14, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Locations

CN (1)