SON-DP in Participants with Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors

Last updated: March 7, 2025
Sponsor: Qurgen Inc.
Overall Status: Active - Recruiting

Phase

1

Condition

Gastric Cancer

Liver Cancer

Stomach Cancer

Treatment

SON-DP

Clinical Study ID

NCT06873659
SON-DP-A003-ST
  • Ages 18-75
  • All Genders

Study Summary

A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SON-DP in Subjects with Advanced Solid Tumors

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Male or female participants aged 18 to 75 years (inclusive).

  2. For Phase Ia: Participants with histologic diagnosis and confirmed solid tumor; ForPhase Ib: Participants with one of the two tumor types: Group 1: advanced primaryliver cancer; Group 2: Advanced primary gastric cancer (including gastroesophagealjunction adenocarcinoma).

  3. There must be at least one measurable lesion defined by RECIST v1.1. Lesionsintended for biopsy should generally not be selected as target lesions, unless theinvestigator assesses that the biopsy of the lesion will not affect subsequent tumorevaluations. Lesions that have previously undergone radiation therapy,interventional therapy, or other local treatments should generally not be selectedas target lesions, unless the lesion shows clear radiological progression afterlocal treatment.

  4. The ECOG performance status ≤ 1.

  5. Able to understand and willing to sign the informed consent form (ICF) and complywith all the requirements of the protocol.

  6. The investigator assesses that the subject's expected lifespan is greater than 3months.

  7. Subjects must be candidates for and agree to the placement of a central venousaccess line and further must be able, in the opinion of the Investigator, to managecare of this line.

  8. Subjects with treated brain metastases are allowed but should be neurologicallystable (for 4 weeks post-treatment as assessed by CNS imaging and prior to studyenrollment) and off steroids for at least 2 weeks before administration of any studytreatment.

  9. All subjects in Phase Ia (with partial exceptions for the first 2 dose levels anddesignated subjects in Phase Ib must be prepared to undergo 2 or more tumorbiopsies, one during the screening period and 1-2 biopsy during therapy. In theInvestigator's assessment, these biopsies should be feasible considered, safe by theinvestigator, and not expected to interfere with all other study assessments.

  10. Adequate hepatic/renal function as evidenced by meeting all the followingrequirements:

  11. Total bilirubin ≤ 1.5 × ULN except for subjects with Gilbert's syndrome who areexcluded if TBIL > 3.0×ULN or direct bilirubin < 1.5×ULN. And there is noevidence of sustained liver function elevation (within 7 days) or acute hepaticdecompensation, as assessed by the investigator.

  12. AST < 3.0×ULN, except for subjects that have tumor involvement of the liver,who are included if AST ≤ 5×ULN. And there is no evidence of sustained liverfunction elevation (within 7 days) or acute hepatic decompensation, as assessedby the investigator.

  13. ALT ≤ 3.0×ULN, except for subjects that have tumor involvement of the liver,who are included if ALT ≤ 5×ULN. And there is no evidence of sustained liverfunction elevation (within 7 days) or acute hepatic decompensation, as assessedby the investigator.

  14. Blood Urea Nitrogen (BUN) < 2.5×ULN.

  15. The calculated creatinine clearance (CrCL) using the Cockcroft-Gault formulamust be ≥ 60 mL/min.

  16. Primary liver cancer: Child-Pugh class A or class B with a score of 7, and nohistory of hepatic encephalopathy.

  17. The subject must have adequate bone marrow function (no blood transfusions orhematopoietic growth factor support within 14 days prior to the first dose ofSON-DP), with special circumstances to be jointly evaluated by the study team,sponsor, and CRO medical team:

  18. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;

  19. Hemoglobin (HGB) ≥ 80 g/L;

  20. Platelet count (PLT) ≥ 75 × 10⁹/L.。

  21. Coagulation tests within an acceptable range defined by the following:

  22. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

  23. International normalized ratio (INR) or Prothrombin Time (PT) ≤ 1.5×ULN.Exception: INR 2 to ≤ 3 ULN is acceptable for subjects on stable therapeuticanticoagulants without active bleeding within 14 days prior to the first doseof the study drug.

  24. Toxicity related to previous antitumor treatments must have returned to baseline or ≤ grade 1 (NCI-CTCAE 5.0), except for toxicities judged by the investigator to poseno safety risk, such as: hair loss, ≤ grade 2 peripheral neuropathy, thyroiddysfunction stabilized by hormone replacement therapy, or other toxicities that arestill grade 2 but are assessed by the investigator as chronic, stable, and with noclear safety concerns.

  25. Female participants must agree not to breastfeed starting at screening andthroughout the study period and for 90 days after final SON-DP administration.

  26. Fertile, eligible subjects (both male and female) must agree to use reliablecontraception methods (hormonal, barrier methods, or abstinence) during the trialand for at least 90 days after the last dose of the medication.

Exclusion

Exclusion Criteria:

  1. Pregnant or breastfeeding women. Pregnancy is defined as the state from conceptionuntil the termination of pregnancy, confirmed by a positive human chorionicgonadotropin (hCG) laboratory test. Unless one of the following criteria is met:permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateraloophorectomy), or documented biological or physiological evidence of postmenopausalstatus (defined as no menstruation for more than 12 months without otherconditions), or women who have been menopausal for 6-12 months must have a serumfollicle-stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause;otherwise, female subjects will be considered fertile.

  2. Participation in an interventional, investigational study within 2 weeks or 5half-lives, whichever is shorter of the first dose of study treatment.

  3. Presence of overt leptomeningeal or active central nervous system (CNS) metastasesor primary tumors or CNS metastases that require local CNS-directed therapy (e.g.,radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2weeks.

  4. Impaired cardiac function or clinically significant cardiac disease, including anyof the following:

  5. Clinically significant and/or uncontrolled heart disease such as congestiveheart failure requiring treatment (New York Heart Association [NYHA] Grade ≥ 2), left ventricular ejection fraction (LVEF) < 50% as determined by multiplegated acquisition (MUGA) or echocardiogram (ECHO), uncontrolled hypertension,or clinically significant arrhythmia.

  6. QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 msECG or congenital long QT syndrome at the Screening Visit, except subjects withpacemaker.

  7. Acute myocardial infarction or unstable angina pectoris < 6 months prior tostudy entry.

  8. Uncontrolled hypertension (systolic blood pressure >160 mmHg and diastolic bloodpressure >100 mmHg), or in the opinion of the Investigator: a recent history ofhypertension crisis, or a recent history of hypertensive encephalopathy.

  9. History of stroke or clinically significant intracranial hemorrhage within 6 monthsbefore first dose of study drug.

  10. Concurrent severe pulmonary diseases, including but not limited to pulmonaryembolism within 3 months prior to enrollment, severe asthma, severe chronicobstructive pulmonary disease (COPD), restrictive lung disease, or pneumoniaconsidered based on imaging examination or investigator assessment at screening, aswell as a history of non-infectious pneumonia requiring steroid treatment within 12months prior to signing informed consent.

  11. Subject with active human immunodeficiency virus (HIV) infection or a history of HIVinfection; subjects with active chronic hepatitis B or active chronic hepatitis C (excluding hepatitis B virus carriers, those with stable hepatitis B after antiviraltreatment [HBV DNA negative/ below the lower limit of detection in hospital'squantitative testing or < 500 IU/mL], and HCV-Ab positive but HCV-RNA negativesubjects); subject with active syphilis.

  12. Other primary malignancies, past or present, except for the enrollment indicationsof this study. However, this does not include: malignancies that have been curedwithin 2 years prior to the first dose of SON-DP with no signs of recurrence, fullytreated and completely resected cervical carcinoma in situ, completely resected skinbasal cell carcinoma or squamous cell carcinoma, any malignancy considered indolentand not requiring treatment, or any type of carcinoma in situ that has beencompletely resected.

  13. The presence of clinically symptomatic, poorly controlled pleural effusion,pericardial effusion, or ascites that requires repeated drainage.

  14. Anticancer therapy within 5 half-lives or 3 weeks (whichever is shorter) prior tostudy entry. Chinese anticancer medicine, three weeks prior first dosing.

  15. Received radical radiation therapy or radiation to an area where the bone marrowproportion is greater than 30% within 4 weeks prior to the first dose of SON-DP.Exceptions include: palliative radiation therapy for localized lesions (e.g.,radiation therapy for bone lesions aimed at symptom relief) or local interventionaltreatments (such as transarterial chemoembolization [TACE] and others) assessed bythe investigator as posing no safety risks.

  16. Subjects receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥ 10 mg/day prednisone or equivalent) two weeks prior first SON-DP dosing. Topical,inhaled, nasal, and ophthalmic steroids are allowed.

  17. The use of any live vaccines or live attenuated vaccines against infectious diseaseswithin 4 weeks prior to the first dose of SON-DP and during the study treatmentperiod.

  18. Subjects with a history of stroke or having active neurological symptoms, with theexception of chronic conditions or sequelae which in the opinion of the neurologist,Investigator, and the Sponsor, would not impact ongoing neurologic assessments whileon study treatment. a) This includes subjects with active sickle-cell disease with CNS involvement andactive intracranial bleeding.

  19. Subjects who are using medications that cannot be used concurrently with urea;subjects who are using medications that require special caution or carefulconsideration when used with urea. Enrollment may be allowed if the investigatorassesses that the risks can be controlled.

  20. Subjects with diseases affecting the thirst recognition center, such as centraldiabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion (SIADH), etc.

  21. Active infection requiring intravenous systemic antibiotic or antiviral therapywithin 14 days prior to the first dose of SON-DP.

  22. Major surgery within 4 weeks of the first dose of study treatment (mediastinoscopy,insertion of a central venous access device, and insertion of a feeding tube are notconsidered major surgery).

  23. Subjects who have undergone solid organ or hematopoietic stem cell transplantationwithin 5 years prior to signing the informed consent for this study.

  24. Any medical condition that would, in the Investigator's judgment, prevent thesubject's participation in the clinical study due to safety concerns, compliancewith clinical study procedures, or interpretation of study results.

  25. Allergy to study protein drug or components of its formulation such as PEI and urea.

  26. History of a Grade 3 to 4 allergic reaction to treatment with another proteinproduct.

Study Design

Total Participants: 96
Treatment Group(s): 1
Primary Treatment: SON-DP
Phase: 1
Study Start date:
February 26, 2025
Estimated Completion Date:
November 30, 2027

Study Description

  • SON-DP is different from the conventional cancer cell-killing therapy which have high side effect, drug resistance, cancer recurrence and tumor heterogenicity, SON-DP is a novel transcription factor (TF) protein anticancer drug to treat the Participants with relapsed and advanced metastatic solid tumors. Proposed as an effective therapeutic drug product for a cell-converting cancer therapy, SON-DP is expected to transform cancer cells in situ into normal tissue cells via a SON-DP induced cancer cell reprogramming and re-differentiation process as an innovative rationale.

  • SON-DP is developed based on the rationale of cancer cell conversion into normal tissue cells as the primary mechanism of actions of a new cancer therapy, not by cancer cell-killing, the traditional goals of chemotherapy, radiation therapy, targeted therapy and immune therapy. Cancer cell conversion is achieved by the SON-DP induced pluripotent re-programming in situ inside tumor tissue into transient iPSCs (tiPSCs) that quickly re-differentiate into normal tissue cells induced by the differentiating resident tissue environment. The in situ generated tiPSCs either secrete exosomes, providing the embryonic stem cells (ESC)-like microenvironments to transform the surrounding cancer cells into normal tissue cells for an overall malignant phenotype reversion (OMPR) (an effect named as a bystander effect), or display a targeting effect that enables the in situ generated tiPSCs to track down the distant metastatic cancer cells for OMPR (an effect named as a tropism effect). The SON-DP-induced cell reprogramming also restored the mutation-caused and compromised p53 checkpoint in cancer cells to re-establish cell quality control system that ensures the downstream re-differentiation of the in situ generated tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming and re-differentiation process is capable of transforming both primary and metastatic cancer cells into normal tissue cells.

    • Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in eradication of late-stage cancers and long term (over 3 years) survival without teratoma formation and cancer recurrence in multiple tumor-bearing mouse/rat (syngeneic) or human xenograft rodent models, providing high treatment efficacy of this cell-converting cancer therapy. Thus, the cell-converting cancer therapy rationale represents a new cancer therapeutic strategy. SON-DP was tolerated in tumor-bearing rodents, as well as in naïve rats, dogs, and monkeys as demonstrated by GLP-enabled (rats and dogs) and non-GLP (monkey) toxicity study and after repeated IV administrations at higher doses compared with the planned clinical dose range. Therefore, the current nonclinical studies, including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies, support the safety and efficacy of SON-DP TF protein drug product to be used in clinical studies of human participants. This clinical study will be conducted in selected types of relapsed/refractory advanced/metastatic solid tumors as a step in demonstrating the utility of this anticancer agent.

    • In this SON-DP-A003-ST clinical trial, SON-DP is given to the participants with late stage solid tumors through 150-minutes IV infusion once a week at 4 dose levels during the first Phase I dose escalation to find the recommended phase II dose (RP2D) for the second Phase Ib does expansion stage that will focus on 2 cancer types including advanced primary liver cancer and advanced primary gastric cancer.

    • During Phase Ia dose escalation stage, an 3+3 design will be followed. Phase Ia will enroll the participants with various types of solid tumors that metastasized and not response to standard treatment.

    • During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to treat the participants with 2 specific cancer types including advanced primary liver cancer and advanced primary gastric cancer. Two groups of cancer cohorts will be opened with eligible participants who have relapsed/refractory/intolerant to standard of care therapies of these two advanced/metastatic solid tumors. Participants will be followed for safety, confirmation of the RP2D, PK, PD, and anti-tumor activity as measured by standard assessment tools.

Connect with a study center

  • Beijing Cancer Hospital

    Beijing, Beijing 100142
    China

    Active - Recruiting

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing, Beijing 100021
    China

    Site Not Available

  • Jiangsu Province Hospital

    Nanjing, Jiangsu 210029
    China

    Active - Recruiting

  • ZhongShan Hospital Fudan University

    Shanghai, Shanghai 200032
    China

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.