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Non-Small Cell Lung CancerPhase 1/2NCT05278364

Phase I/II Study of SY-5007, a RET Inhibitor, in Patients With RET-altered Advanced Solid Tumor

A Phase 1/2 study testing SY-5007 in people with Non-Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Shouyao Holdings (Beijing) Co. LTD at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a phase I/II, open-label, multi-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of SY-5007 administered orally to participants with advanced solid tumors, including RET Fusion-Positive NSCLC or RET-mutated MTC or other… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SY-5007
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
184 participants
Where
2 sitesChina
Study dates
23 Apr 2021to 10 Feb 2025
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • -
  • For Phase I:
  • Male or female, at least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
  • Estimated life expectancy >12 weeks.
  • Patients must have at least one assessable lesion in dose-escalation part and one measurable lesion in dose-expansion part per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
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  • Dose-escalation Part: patients must have histological or cytological confirmed advanced solid tumours with RET alteration (fusion or mutation) and have progressed after standard therapy, or no standard or available curative therapy exists.
  • Dose-expansion Part: Patients with advanced tumor must have histological or cytological confirmed RET alteration, including NSCLC patients with RET-fusion or MTC patients with RET-mutation or other patients with RET alteration, and either have progressed after standard therapy or no standard/ available curative therapy exists.
  • Patients must have adequate organ function as defined in the below:
  • Hepatic function:
  • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN) if no hepatic metastases are present, or otherwise ≤ 5 times ULN, Total serum bilirubin (TBIL) ≤ 1.5 times ULN.
  • Bone marrow function (No blood transfusion or haematopoietic stimulating factor treatment within 10 days prior to testing):
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L; Platelets (PLT) count ≥ 75 x 10⁹/L; Hemoglobin (Hb) ≥ 85 g/L.
  • Renal function:
  • Creatinine clearance ≥ 50 mL/min.
  • Coagulation function:
  • Prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.5 times ULN.
  • Serum lipid:
  • Cholesterol ≤ 500mg/dL(12.92mmol/L).
  • Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the first dose, male and female patients of childbearing potential must be willing to completely abstain 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.
  • For Phase II: As for phase I with the following modifications:
  • Participants must have histological or cytological confirmed locally advanced or metastatic RET Fusion-Positive NSCLC, have progressed following platinum-based chemotherapy and/or PD-1/PD-L1 immunotherapy, or have not received prior systemic therapy, or in the opinion of the Investigator, they would be unlikely to tolerate or derive significant clinical benefit from appropriate standard of care therapy, or they declined standard therapy.
  • The participants' tumor tissue or blood sample test results meet 1 of the following 2 criteria:
  • Previous tumor tissue or blood sample confirmed positive for RET fusion by local laboratory.
  • If no previous positive RET fusion test report is available, a compliant tumor tissue or blood sample must be tested at a central laboratory designated by the sponsor, using a second-generation sequencing (NGS)-based assay, and confirmed as positive for RET fusion.

Who cannot join

  • Dose-expansion Part: Patient's cancer has a known primary driver alteration other than RET. e.g. EGFR, ALK, ROS1, KRAS, etc.
  • Dose-expansion Part: Patients previously treated with a selective RET inhibitor.
  • Patients received systemic antitumor therapy, including chemotherapy, radiotherapy, biologic therapy, endocrine therapy, or immunotherapy within 3 weeks prior to the first dose, except for the following:
  • Nitrosoureas or mitomycin C within 6 weeks; Oral fluorouracils and small molecule drugs within 2 weeks or within 5 half-life periods of the drug (whichever is longer); Antitumour traditional Chinese medicine within 2 weeks.
  • Patients received other unlisted clinical trial drugs or treatments within 4 weeks prior to the first dose.
  • Patients underwent major organ surgery (excluding puncture biopsy) or had significant trauma within 4 weeks prior to the first dose.
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  • Adverse effects of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade rating of ≤ grade 1 (except for toxicity judged by the investigator be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.)
  • Patients have symptomatic central nervous system (CNS) metastases, meningeal metastases, or a primary CNS tumor that is associated with progressive neurological symptoms.
  • Patients with active uncontrolled systemic bacterial, viral, or fungal infection despite optimal treatment (chronic disease screening not required).
  • Active hepatitis (Hepatitis B: HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL; Hepatitis B: HCV antibody-positive and HCV-RNA ≥ 1000 IU/ml), HIV antibody-positive; Active syphilis.
  • Patients have a history of severe cardiovascular disease, including but not limited to:
  • Severe cardiac rhythm or conduction abnormalities, e.g. ventricular arrhythmia requiring clinical intervention, II-III degree atrioventricular block, etc.
  • Mean QT interval corrected using Fridericia's formula (QTcF)> 480ms at rest. Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke or other grade 3 or higher cardiovascular or cerebrovascular events within 6 months prior to the first dose.
  • New York Heart Association (NYHA) ≥ class II heart failure or left ventricular ejection fraction (LVEF) < 50%.
  • Hypertension remains uncontrolled after aggressive antihypertensive therapy.
  • Patients have been treated with any CYP3A inhibitors or inducers within 14 days prior to the first dose.
  • Patients with malignancies other than tumors treated in this study (except: malignancies that are cured and have not recurred within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type).
  • Patients are unable to swallow the drug orally, or has a condition that seriously affects gastrointestinal absorption in the judgment of the investigator.
  • For Phase II: As for phase I with the following modifications:
  • Patients received any selective RET inhibitor (including marketed drugs such as selpercatinib, pralsetinib, and unmarketed experimental drugs).
  • Patients have a history of hypersensitivity to any component or excipient of SY-5007 capsule.
  • Patients participated in another clinical study within 4 weeks prior to the first dose or is scheduled to participate in another clinical study during the study period.
  • Pregnant or breastfeeding female patients.
  • Other conditions deemed by the investigator to be inappropriate for participation in this clinical trial.

Trial locations and contacts

2 sites in 1 country.

Yinghui Sun, PhD contact

86-10-88858616

yhsun@centaurusbio.com

China2 sites, 2 recruiting
  • Shanghai Pulmonary Hospital

    Shanghai, Shanghai Municipality, 200433

    Caicun Zhou, PhD, 13301825532, caicunzhoudr@163.com

    Recruiting
  • Tianjin People's Hospital

    Tianjin, Tianjin Municipality, 300000

    Ming Gao, PhD, Headandneck2008@126.com

    Recruiting

Other trials in China

About this study

Official title: A Phase I/II, Open-Label, Single-arm, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antineoplastic Activity of SY-5007 in Patients With RET-altered Advanced Solid Tumor.

This is a phase I/II, open-label, multi-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of SY-5007 administered orally to participants with advanced solid tumors, including RET Fusion-Positive NSCLC or RET-mutated MTC or other RET-altered advanced solid tumor.

Read the detailed description

The study consists of 2 parts:

Part 1: Dose-escalation and dose-expansion in patients with RET Fusion-Positive NSCLC or RET-mutated MTC or other RET-altered advanced solid tumor. Dose-escalation study phase is designed to determine the DLTs (Dose-limiting toxicity) and recommended phase II dose (RP2D) and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of SY-5007. Dose-expansion study phase is designed to evaluate the antitumor activity (ORR, DCR and DoR) of SY-5007 in patients.

Part 2: Phase II study to evaluate the antitumor efficacy of SY-5007. Patients with advanced RET Fusion-Positive NSCLC will be enrolled in this phase. SY-5007 will be administered orally 160mg twice daily in a 28-day cycle. This phase is designed to determine the antitumor activity (ORR, DCR, DoR, PFS and OS), safety, and PK of SY-5007.

Being tested
SY-5007
Keywords
SY-5007, RET-fusion positive NSCLC, RET-mutant MTC, RET-altered advanced solid tumor
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Medullary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SY-5007Drug

    Also called SY-5007 Capsule

    a RET selective Inhibitor

Study groups in NCT05278364
Study groupRoleWhat they receive
Dose-escalation and Dose-expansionExperimentalDose-escalation Phase: Multiple doses of SY-5007 for oral administration. Dose Expansion Phase: RP2D of SY-5007 as determined during Dose Escalation.
Receives: Drug: SY-5007

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Determine the dose-limiting toxicities (DLT) during the first 28-day cycle of SY-5007 treatment

    Maximum Tolerated Dose (MTD) and/or recommended phase 2 dose (RP2D) in Cycle 1

    Measured: Dose-escalation Cycle 1 (each cycle is 28 days)

  2. Phase I: Number of patients with adverse events and serious adverse events

    Characterization of the safety and tolerability

    Measured: Up to 24 months

  3. Phase II: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

    Anti-tumor activity of SY-5007

    Measured: Up to 24 months

Secondary outcomes (10)
  1. Phase I: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteriaOverall Response Rate (ORR) as assessed by RECIST 1.1 criteria

    Preliminary anti-tumor activity of SY-5007

    Measured: Up to 24 months

  2. Phase I & II: Disease control rate (DCR) as assessed by RECIST 1.1 criteria

    Preliminary anti-tumor activity of SY-5007

    Measured: Up to 24 months

  3. Phase I & II: Duration of response (DOR)

    Preliminary anti-tumor activity of SY-5007

    Measured: Up to 24 months

  4. Phase I & II: Progression Free Survival (PFS)

    Preliminary anti-tumor activity of SY-5007

    Measured: Up to 24 months

  5. Phase I & II: Overall survival (OS)

    Anti-tumor activity of SY-5007

    Measured: Up to 24 months

  6. Phase I & II: Percentage of Participants with any Serious Adverse Events (SAEs)

    Characterization of the safety and tolerability

    Measured: Up to 24 months

  7. Phase I & II: Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)

    Cmax of SY-5007

    Measured: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject

  8. Phase I & II: Pharmacokinetic Parameters Including time to maximum plasma concentration (Tmax) of SY-5007

    Tmax of SY-5007

    Measured: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject

  9. Phase I & II: Pharmacokinetic Parameters Including Area Under the Plasma Concentration-Time Curve of SY-5007 (AUC)

    AUC of SY-5007

    Measured: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject

  10. Phase I & II: Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2) of SY-5007

    plasma terminal phase disposition half-life of SY-5007

    Measured: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2022
  2. Study start23 Apr 2021
  3. Primary completion1 Jan 2025 (estimated)
  4. Study completion10 Feb 2025 (estimated)

Resources

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
184 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05278364
Sponsor's protocol ID
SY-5007-I
Status last verified
Apr 2023
First submitted
8 Mar 2022
Last updated
12 Apr 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Li W, Wang Y, Xiong A, Gao G, Song Z, Zhang Y, Huang D, Ye F, Wang Q, Li Z, Liu J, Xu C, Sun Y, Liu X, Zhou F, Zhou C. First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors. Signal Transduct Target Ther. 2024 Nov 4;9(1):300. doi: 10.1038/s41392-024-02006-9.

    PubMed 39489747

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SY-5007 in people with Non-Small Cell Lung Cancer and Medullary Thyroid Cancer, 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 26 inclusion and 24 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 12 Apr 2023. 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?

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?

Phase I: Determine the dose-limiting toxicities (DLT) during the first 28-day cycle of SY-5007 treatment (time frame: Dose-escalation Cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05278364, which also lists 1 linked publication.

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 12 Apr 2023.

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