ALK Positive Advanced MalignanciesPhase 1/2NCT07810933
A Phase 1/2 Study of SY-12321 in Patients With ALK-positive Advanced Malignancies
A Phase 1/2 study testing SY-12321 in people with ALK Positive Advanced Malignancies, run by Shouyao Holdings (Beijing) Co. LTD at 2 sites in China.
Trial summary
A phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of SY-12321 in trial participants with ALK-positive advanced malignancies, including non-small cell lung cancer (NSCLC), inflammatory myofibroblastic tumor (IMT), anaplastic large-cell lymphoma (ALCL)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALK Positive Advanced Malignancies
- What is being tested?
- SY-12321
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 2 sitesChina
- Study dates
- 12 Aug 2026to Aug 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Trial participant voluntarily participates in this study and provides signed written informed consent form (ICF).
- Histologically or cytologically confirmed advanced malignancy (locally advanced unresectable or metastatic).
- Trial participant is aged ≥ 18 years at the time of signing the ICF.
- For trial participants previously treated with an ALK-TKI: subjects are eligible for enrollment if they have a report of ALK-positive result from local laboratory testing [fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC) (Ventana assay), reverse-transcription polymerase chain reaction (RT-PCR), next-generation sequencing (NGS), and other assays] using tumor tissue or blood sample obtained within 1 year prior to informed-consent signature. In the absence of such positive report, subjects must provide either non-irradiated archival tissue (collected within 1 year) or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity (ALK fusion and/or other meaningful mutations) must be confirmed by NGS testing performed at the central laboratory for eligibility. For trial participants with no prior ALK-TKI treatment: subjects are eligible for enrollment if they have a prior report of ALK-positive result from local laboratory testing of tumor tissue or blood sample. In the absence of such positive report, subjects must provide either non-irradiated archival tissue or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity must be confirmed by NGS testing performed at the central laboratory for eligibility.
- Note: Requirements for tumor tissue and blood sample testing are detailed in the Central Laboratory Operations Manual.
- Phase Ia will enroll trial participants with ALK-positive advanced malignancies who are pretreated. Pretreated is defined as disease progression or intolerance following standard systemic anti-tumor therapy for advanced disease (recommended by clinical oncology practice standards including Chinese Society of Clinical Oncology (CSCO) guidelines and expert consensus); intolerance is defined as recurrence of Grade ≥3 adverse events despite adequate symptomatic treatment with well-documented evidences (corresponding laboratory findings or original medical records from that episode). Phase Ib will enroll two cohorts: Cohort 1: ALK-positive advanced NSCLC previously treated with any second- and/or third-generation ALK-TKI (including investigational agents not yet marketed); Cohort 2: Other pretreated ALK-positive advanced malignancies. Phase Ⅱ will enroll five cohorts: Cohort 1: ALK-positive advanced NSCLC previously treated with any second-generation ALK-TKI (including investigational agents not yet marketed); Cohort 2: ALK-positive advanced NSCLC previously treated with any third-generation ALK-TKI (including investigational agents not yet marketed); Cohort 3: ALK-positive advanced NSCLC previously treated with both second- and third-generation ALK-TKIs (including investigational agents not yet marketed); Cohort 4: ALK-positive advanced NSCLC without prior exposure to any ALK-TKI (including investigational agents not yet marketed); Cohort 5: Other ALK-positive advanced malignancies.
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- At least one measurable extracranial target lesion per RECIST Version 1.1 (for solid tumors) or other standard tumor response assessment criteria (e.g., the Lugano criteria for trial participants with lymphoma). For previously irradiated lesions, such lesions may serve as target lesions only if clear progression has occurred after radiotherapy.
- Expected survival > 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- 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 if liver metastasis or Gilbert's syndrome is present.
- Pancreatic function: serum total amylase ≤ 1.5 × upper limit of normal (ULN); serum lipase ≤ 1.5 × ULN. (If serum total amylase > 1.5 × ULN: enrollment is permitted provided that the trial participant is willing to undergo additional pancreatic amylase testing and the result is within the ULN; enrollment is not allowed if a pancreatic-amylase result within the ULN cannot be obtained.) Bone marrow function (No blood products, hematopoietic growth factors, or other treatments for hematological abnormalities within 7 days prior to testing): Absolute neutrophil count (ANC) ≥ 1.5×10^9/L. Platelet count (PLT) ≥ 75×10^9/L. Hemoglobin (Hb) ≥ 90 g/L.
- Renal function: Creatinine level less than 1.5×upper limit of normal (ULN) or Creatinine clearance ≥ 50 mL/min (according to the Cockcroft and Gault formula).
- Coagulation function: Prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.5× ULN (except for subjects on anticoagulation therapy).
- 10.Female participants of child-bearing potential must have a negative serum pregnancy test result within 7 days prior to the first study drug administration. Male/female participants with reproductive potential and their partners agree to use highly effective contraceptive measures from the time of screening until at least 3 months after the last study drug dose [1. Abstinence (acceptable only if it is part of the participant's usual lifestyle); 2. Hormonal contraception (oral, patch, ring, injection, implant) combined with male condoms. This contraceptive method must be initiated at least 30 days before the first study drug administration; otherwise, another acceptable contraceptive method shall be adopted; 3. Intrauterine device combined with male condoms].
Who cannot join
- Presence of known major driver gene alterations (identified in the participant's current genetic testing report) other than ALK, including but not limited to EGFR, MET (note: including overexpression), ROS1, RET, NTRK, KRAS, etc. For other co-mutation profiles, enrollment eligibility may be discussed with the sponsor.
- Prior treatment with any fourth-generation ALK inhibitors (including investigational agents).
- Known history of allergy to any active ingredient or excipient in SY-12321 capsules.
- Received the following treatments prior to the first dose of SY-12321 capsules:
- Nitrosoureas or mitomycin C administered < 6 weeks before the first dose of study drug; platinum agents, pemetrexed, paclitaxel and other chemotherapeutic agents administered < 2 weeks (or 5 half-lives, whichever is shorter) before the first dose of study drug; small-molecule targeted agents administered < 2 weeks (or 5 half-lives, whichever is shorter) before the first dose of study drug; anti-tumor hormonal therapy, traditional Chinese medicines/Chinese patent medicines with anti-tumor indications administered < 2 weeks before the first dose of study drug; radiotherapy administered < 4 weeks before the first dose of study drug (or < 2 weeks for palliative stereotactic radiotherapy not involving the chest, abdomen or pelvis); immunotherapy, biotherapy, and other investigational medicinal products administered < 4 weeks before the first dose of study drug; radioactive seed implantation, radionuclide therapy, and cell therapy (e.g., CAR-T, stem-cell transplantation, etc.) administered < 3 months before the first dose of study drug; major surgical procedures (excluding central venous catheter placement, bone-marrow aspiration and biopsy, and gastric tube placement) performed < 4 weeks before the first dose of study drug.
- Adverse reactions from prior anti-tumor therapy have not recovered to Grade ≤ 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 6.0 (except for toxicities judged by the investigator to pose no safety risk, such as alopecia, Grade 2 peripheral neuropathy, and specific laboratory parameters specified in Inclusion Criterion 9).
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- Presence of other malignant neoplasms apart from the tumor under investigation in this study (exceptions: malignancies cured with no recurrence within 2 years prior to study enrollment; completely resected basal-cell and squamous-cell skin carcinoma; completely resected in-situ carcinoma of any type).
- Severe gastrointestinal disorders, including active ulcerative colitis, Crohn's disease, peptic ulcer, gastrointestinal perforation or acute gastrointestinal hemorrhage, or dysphagia, or prior surgical procedures that may substantially impair drug absorption.
- Symptomatic or clinically unstable primary central nervous system (CNS) tumor/metastases, carcinomatous meningitis, leptomeningeal carcinomatosis/metastases, or spinal-cord compression. Note: Stable CNS disease is defined as no radiological evidence of progression (new or enlarging brain metastases) for at least 4 weeks prior to the first study drug dose; no CNS surgery within 4 weeks before first dosing; no whole-brain radiotherapy within 4 weeks before first dosing; no stereotactic radiosurgery (SRS) within 2 weeks before first dosing; and symptomatic treatments such as steroids and mannitol have been discontinued for 2 weeks or maintained at a stable dose before first dosing.
- Presence of Grade ≥ 2 cataract, or Grade ≥ 2 keratitis/corneal ulcer.
- Active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose of investigational medicinal product.
- Active hepatitis B: positive hepatitis B surface antigen (HBsAg) with HBV-DNA ≥2000 IU/mL; active hepatitis C: positive HCV antibody with HCV-RNA ≥1000 IU/mL); active syphilis (dual-positive for non-treponemal and treponemal syphilis antibodies); positive HIV antibody, or known history of other immunodeficiency disorders; or prior history of organ transplantation, hematopoietic stem-cell transplantation or bone-marrow transplantation (excluding prior hematopoietic stem-cell transplantation in patients with ALCL).
- Within 3 months prior to signing the informed consent form, presence of severe pulmonary diseases (excluding malignancy) requiring systemic therapy, such as active pulmonary tuberculosis, interstitial lung disease, etc.
- Well-documented prior history of neurological or psychiatric disorders, such as dementia.
- History or abnormalities of severe cardiovascular and cerebrovascular diseases, including but not limited to:
- Severe cardiac rhythm or conduction abnormalities, e.g., clinically significant ventricular arrhythmias requiring intervention, grade II-III atrioventricular block; Resting Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 msec (male). (If QTcF prolongation is suspected to be drug-induced, participants may be enrolled after pharmacological correction if assessed to be safe and manageable by the investigator); < 6 months since previous coronary angioplasty or stent implantation; Severe aortic valve stenosis; New York Heart Association (NYHA) class ≥ II heart failure or left ventricular ejection fraction (LVEF) < 50%; Occurrence of acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade ≥ 3 cardiovascular-cerebrovascular events within 6 months prior to the first study drug dose; Radiological evidence of central nervous system hemorrhage (participants with resolved asymptomatic grade 1 post-surgical hemorrhage sustained for > 3 months may be enrolled).
- Severe thrombosis, coagulopathy or bleeding diathesis, including arterial or venous thromboembolic events within 6 months before the first dose of investigational medicinal product [including history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep-vein thrombosis, or any other severe thromboembolic events (excluding muscular calf vein thrombosis)]; any life-threatening bleeding events (requiring blood transfusion, surgical or local intervention, or continuous medical therapy); or lesion invasion of large blood vessels judged by the investigator to confer bleeding risk (excluding lesions encircling less than two-thirds of the vessel circumference).
- Uncontrolled hypertension despite optimal antihypertensive therapy, defined as a mean systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg obtained from three repeated measurements separated by at least 10 minutes.
- Poorly controlled diabetes mellitus [fasting blood glucose ≥10 mmol/L and/or glycated hemoglobin (HbA1c) ≥8%. Glycated hemoglobin testing is mandatory for patients with a history of diabetes mellitus and optional for patients without].
- Poorly controlled pleural effusion, ascites or pericardial effusion (poorly controlled is defined as obvious increase in effusion within 2 weeks prior to the first dose of investigational medicinal product, presence of prominent symptoms, or requirement for paracentesis or other interventions).
- Symptomatic hyperthyroidism or hypothyroidism that cannot be controlled as assessed by the investigator.
- Electrolyte disturbances (e.g., hypocalcemia, hypomagnesemia, hypokalemia) that cannot be controlled as assessed by the investigator.
- Use of strong CYP3A inhibitors or strong CYP3A inducers within 1 week prior to the first dose of investigational medicinal product or within 5 half-lives (of strong CYP3A inhibitors or inducers), whichever is longer; or anticipated need for such agents during the study period.
- Pregnant or lactating female subjects.
- Presence of other underlying diseases or medical conditions that may increase the risks associated with investigational medicinal product administration, place the participant at undue risk, confound the interpretation of adverse reactions or adverse events (AEs) of the investigational medicinal product; or poor participant compliance; or any other conditions rendering the participant unsuitable for enrollment as judged by the investigator.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Li Zhang MD, MD, 86+020 87343458, zhangli6@mail.sysu.edu.cn
- Recruiting
The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu
Yongsheng Wang MD, MD, 86+025 6958 8476, 15150580136@163.com
About this study
Official title: An Open-label, Multicenter Phase Ⅰ/Ⅱ Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SY-12321 in Patients With ALK-positive Advanced Malignancies
A phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of SY-12321 in trial participants with ALK-positive advanced malignancies, including non-small cell lung cancer (NSCLC), inflammatory myofibroblastic tumor (IMT), anaplastic large-cell lymphoma (ALCL), colorectal cancer, pancreatic cancer, breast cancer, and others.
Read the detailed description
This is an open-label, multicenter Phase 1/2 clinical trial consisting of three cohorts: In Phase Ia, a dose-escalation study will be conducted in trial participants starting at 10 mg once daily (QD) (dose level 1) to explore the maximum tolerated dose (MTD) and determine recommended doses for expansion (RDEs). In Phase Ib, a dose-expansion study will be performed in trial participants at one or two RDEs, where the recommended Phase 2 dose (RP2D) will be identified based on safety, pharmacokinetic (PK) data, and preliminary efficacy. In Phase Ⅱ, further efficacy exploration will be carried out in trial participants treated at the RP2D. Trial participants in this study will receive SY-12321 until disease progression (PD), intolerable toxicity, death, or occurrence of other treatment-discontinuation criteria.
- Conditions
- ALK Positive Advanced Malignancies
- Being tested
- SY-12321
- Keywords
- SY-12321, Shouyao holdings, ALK positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SY-12321Drug
A fourth-generation ALK tyrosine kinase inhibitor (Other Names: SY-12321 capsules)
| Study group | Role | What they receive |
|---|---|---|
| Experimental: SY-12321 | Experimental | Dose-escalation, Dose-expansion and further efficacy exploration. In dose-escalation phase, SY-12321 capsules will be administrated orally, repeat daily, 21 days as a dosing cycle, in ascending doses. In dose-expansion phase, one or two RDEs of SY-12321 determined in dose-escalation phase will be administrated orally, repeat daily, 21 days as a dosing cycle. In further efficacy exploration, RP2D of SY-12321 determined in dose-escalation phase will be administrated orally, repeat daily, 21 days as a dosing cycle. Receives: Drug: SY-12321 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose-limiting toxicities (DLTs) in Dose-escalation
Number of participants with DLTs
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days)
MTD
The maximum tolerated dose
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days)
Number of participants with adverse events
Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v6.0 criteria
Measured: Up to 24 months
Recommended Phase 2 Dose (RP2D) in phase Ⅱ
The RP2D will be determined based on efficacy and safety profiles across all dose groups in this phase I study.
Measured: Up to 24 months
Secondary outcomes (9)
Pharmacokinetics (Cmax)
Defined as maximum observed plasma concentration of investigational drugs
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (Tmax)
Defined as time to maximum plasma concentration of investigational drugs
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (AUC0-t)
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of investigational drugs
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (t½)
Defined as the apparent plasma terminal phase disposition half-life of investigational drugs
Measured: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Overall Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of subjects with confirmed CR or PR as best overall response (BOR)
Measured: Up to 24 months
Duration of response (DOR)
Duration of response (DOR) is defined as the time from the first documentation of complete response (CR) or partial response (PR) to the first documentation of PD or death from any cause
Measured: Up to 24 months
Disease control rate (DCR)
Disease control rate (DCR) is defined as the proportion of subjects achieving CR, PR, or stable disease (SD)
Measured: Up to 24 months
Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of first study drug administration to the occurrence of progressive disease (PD) or death from any cause, whichever comes first
Measured: Up to 24 months
Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of first study drug administration to death from any cause
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 posted9 Sep 2026
- Study start12 Aug 2026
- Primary completionAug 2028 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALK Positive Advanced MalignanciesStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07810933
- Sponsor's protocol ID
- SY-12321-I-01
- Status last verified
- Sep 2026
- First submitted
- 2 Sep 2026
- Last updated
- 9 Sep 2026
- 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 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Phase Ⅰ/Ⅱ Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SY-12321 in Patients With ALK-positive Advanced Malignancies
- ClinicalTrials.gov ID
- NCT07810933
- Acronym / sponsor ID
- SY-12321-I-01
- Conditions
- ALK Positive Advanced Malignancies
- Keywords
- SY-12321, Shouyao holdings, ALK positive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Shouyao Holdings (Beijing) Co. LTDUniversity, hospital or other
- Study start
- 12 Aug 2026 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 9 Sep 2026 (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.
A phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of SY-12321 in trial participants with ALK-positive advanced malignancies, including non-small cell lung cancer (NSCLC), inflammatory myofibroblastic tumor (IMT), anaplastic large-cell lymphoma (ALCL), colorectal cancer, pancreatic cancer, breast cancer, and others.
Detailed description
This is an open-label, multicenter Phase 1/2 clinical trial consisting of three cohorts: In Phase Ia, a dose-escalation study will be conducted in trial participants starting at 10 mg once daily (QD) (dose level 1) to explore the maximum tolerated dose (MTD) and determine recommended doses for expansion (RDEs). In Phase Ib, a dose-expansion study will be performed in trial participants at one or two RDEs, where the recommended Phase 2 dose (RP2D) will be identified based on safety, pharmacokinetic (PK) data, and preliminary efficacy. In Phase Ⅱ, further efficacy exploration will be carried out in trial participants treated at the RP2D. Trial participants in this study will receive SY-12321 until disease progression (PD), intolerable toxicity, death, or occurrence of other treatment-discontinuation criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: SY-12321 | Experimental | Drug: SY-12321Dose-escalation, Dose-expansion and further efficacy exploration. In dose-escalation phase, SY-12321 capsules will be administrated orally, repeat daily, 21 days as a dosing cycle, in ascending doses. In dose-expansion phase, one or two RDEs of SY-12321 determined in dose-escalation phase will be administrated orally, repeat daily, 21 days as a dosing cycle. In further efficacy exploration, RP2D of SY-12321 determined in dose-escalation phase will be administrated orally, repeat daily, 21 days as a dosing cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Trial participant voluntarily participates in this study and provides signed written informed consent form (ICF).
- Histologically or cytologically confirmed advanced malignancy (locally advanced unresectable or metastatic).
- Trial participant is aged ≥ 18 years at the time of signing the ICF.
- For trial participants previously treated with an ALK-TKI: subjects are eligible for enrollment if they have a report of ALK-positive result from local laboratory testing [fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC) (Ventana assay), reverse-transcription polymerase chain reaction (RT-PCR), next-generation sequencing (NGS), and other assays] using tumor tissue or blood sample obtained within 1 year prior to informed-consent signature. In the absence of such positive report, subjects must provide either non-irradiated archival tissue (collected within 1 year) or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity (ALK fusion and/or other meaningful mutations) must be confirmed by NGS testing performed at the central laboratory for eligibility. For trial participants with no prior ALK-TKI treatment: subjects are eligible for enrollment if they have a prior report of ALK-positive result from local laboratory testing of tumor tissue or blood sample. In the absence of such positive report, subjects must provide either non-irradiated archival tissue or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity must be confirmed by NGS testing performed at the central laboratory for eligibility.
- Note: Requirements for tumor tissue and blood sample testing are detailed in the Central Laboratory Operations Manual.
Key exclusion criteria (25 listed)
- Presence of known major driver gene alterations (identified in the participant's current genetic testing report) other than ALK, including but not limited to EGFR, MET (note: including overexpression), ROS1, RET, NTRK, KRAS, etc. For other co-mutation profiles, enrollment eligibility may be discussed with the sponsor.
- Prior treatment with any fourth-generation ALK inhibitors (including investigational agents).
- Known history of allergy to any active ingredient or excipient in SY-12321 capsules.
- Received the following treatments prior to the first dose of SY-12321 capsules:
- Nitrosoureas or mitomycin C administered < 6 weeks before the first dose of study drug; platinum agents, pemetrexed, paclitaxel and other chemotherapeutic agents administered < 2 weeks (or 5 half-lives, whichever is shorter) before the first dose of study drug; small-molecule targeted agents administered < 2 weeks (or 5 half-lives, whichever is shorter) before the first dose of study drug; anti-tumor hormonal therapy, traditional Chinese medicines/Chinese patent medicines with anti-tumor indications administered < 2 weeks before the first dose of study drug; radiotherapy administered < 4 weeks before the first dose of study drug (or < 2 weeks for palliative stereotactic radiotherapy not involving the chest, abdomen or pelvis); immunotherapy, biotherapy, and other investigational medicinal products administered < 4 weeks before the first dose of study drug; radioactive seed implantation, radionuclide therapy, and cell therapy (e.g., CAR-T, stem-cell transplantation, etc.) administered < 3 months before the first dose of study drug; major surgical procedures (excluding central venous catheter placement, bone-marrow aspiration and biopsy, and gastric tube placement) performed < 4 weeks before the first dose of study drug.
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-12321A fourth-generation ALK tyrosine kinase inhibitor (Other Names: SY-12321 capsules) | Drug | Experimental: SY-12321 |
Primary outcome
Incidence of Dose-limiting toxicities (DLTs) in Dose-escalation
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days)
Number of participants with DLTs
MTD
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days)
The maximum tolerated dose
Number of participants with adverse events
Time frame: Up to 24 months
Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v6.0 criteria
Recommended Phase 2 Dose (RP2D) in phase Ⅱ
Time frame: Up to 24 months
The RP2D will be determined based on efficacy and safety profiles across all dose groups in this phase I study.
9 secondary outcomes
Pharmacokinetics (Cmax)
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (Tmax)
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (AUC0-t)
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Pharmacokinetics (t½)
Time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days) In dose-escalation, 21 days after the first dose in Dose-expansion
Overall Response Rate (ORR)
Time frame: Up to 24 months
Duration of response (DOR)
Time frame: Up to 24 months
Disease control rate (DCR)
Time frame: Up to 24 months
Progression-free survival (PFS)
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SY-12321 in people with ALK Positive Advanced Malignancies, run by Shouyao Holdings (Beijing) Co. LTD at 2 sites 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 15 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chenjie Tang Manager (86+010-88858866, cjtang@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) in Dose-escalation (time frame: 28 days after the first dose (single dose for 7 days and dose-escalation cycle 1 for 21 days)). The study lists 4 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 9 Sep 2026.