Safety and Efficacy of Recombinant Oncolytic Adenovirus L-IFN Injection in Relapsed/Refractory Solid Tumors Clinical Study

NCT05180851 | Unknown Early Phase 1

• 1 other identifier: YSCH-01-0000
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, dose escalation study of the safety and tolerability of Recombinant oncolytic adenovirus L-IFN injection（YSCH-01） when administered via intratumoral injection in patients with advanced solid tumors. The purpose of this study is to assess the safety and tolerability of Recombinant L-IFN adenovirus injectionand to determine the recommended phase 1 dose for further study. The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of Recombinant L-IFN adenovirus injection

Conditions

Head and Neck Cancer; Melanoma; Breast Cancer; Bladder Cancer; Ovarian Carcinoma; Cervical Carcinoma; Lung Cancer

Keywords

Cancer targetting gene-virotherapy(CTGVT) virus (YSCH-01); Oncolytic virus; Oncolytic adenovirus; Replicative adenovirus

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

  To define the maximum tolerated dose (MTD) of intratumoral administration of Recombinant L-IFN adenovirus injection in humans with malignant tumors.

  Up to 28 days

• Safety and tolerability assessed by Adverse Events (AEs)

  An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP

  Time Frame: Up to 6 months

Secondary Outcomes (3)

• Number of participants with vital sign abnormalities and /or adverse event

  Up to 6 months

• Number of participants with laboratory value abnormalities and/or adverse events

  Up to 6 months

• Presence of neutralizing antibodies of antidrug antibodies (ADAs) development

  Up to 6 months

Study Arms (1)

Safety and efficacy of recombinant L-IFN adenovirus injection in relapsed/refractory solid tumors

EXPERIMENTAL

1.Only 1 lesion: If the tumor volume is less than or equal to 10 cm3, the whole tumor is injected radially and evenly. If the tumor volume was \>10 cm3, the tumor was evenly divided into five quadrants and injected into one quadrant at a time. 2\. If there are 2 or more lesions, the most manageable tumor injection is selected; 3. Priority should be given to the body surface metastases that meet the evaluation criteria for tumor efficacy. 4\. According to patients' conditions (e.g., patients with thorax and ascites), the investigator and the research group and cooperative units jointly explored other drug administration approaches (e.g., bladder infusion, thorax and abdominal cavity administration)

Drug: Recombinant L-IFN adenovirus injection

Interventions

Recombinant L-IFN adenovirus injection DRUG

Before use, dilute the product with normal saline according to the size of the tumor to an appropriate volume (10-30% of the total volume of the tumor), or adjust appropriately according to the specific tumor situation, inject directly into the tumor or inject under the guidance of B ultrasound /CT, inject the drug solution into the tumor edge and tumor evenly

Also known as: (YSCH-01), Cancer targetting gene-virotherapy(CTGVT) virus (YSCH-01), Replicative adenovirus, Oncolytic virus, Oncolytic adenovirus

Safety and efficacy of recombinant L-IFN adenovirus injection in relapsed/refractory solid tumors

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥ 18 and ≤ 75 years;
• Patients with advanced malignant solid tumors, histologically or cytologically confirmed, who have failed standard therapy, have no standard therapy, are not eligible for standard therapy at this stage, or have refused standard therapy；
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the length of non-lymph node lesion ≥10 mm or the short diameter of lymph node lesion ≥15 mm according to CT or MRI cross-sectional images;CT scan of the longest axis of measurable lesions ≥10 mm (CT scan thickness ≤5 mm)；
• There were injectable tumor lesions that met the requirements of the current dose group, including superficial lesions and deep lesions that could be injected under the guidance of B-ultrasound /CT；
• ECOG score of 0 \~ 2;
• Sufficient hematopoietic capacity: ANC ≥1.0 ×10\^9/L (no short-acting albino within 1 week, no long-acting albino within 2 weeks), platelet count ≥75 ×10\^9/L, HGB \> 80 g/L (no blood transfusion within 2 weeks)；
• Adequate liver and kidney function: AST and ALT ≤3 times ULN in patients without liver metastasis, ≤5 times ULN in patients with liver metastasis; Total bilirubin ≤1.5 ULN (excluding hyperbilirubinemia or hyperbilirubin of non-liver origin);Creatinine ≤2.0 ULN and creatinine clearance and creatinine clearance ≥40 mL/min;
• Eligible and fertile patients (male and female) must agree to use a reliable contraceptive method during the trial and for at least 90 days after the last dose; Women of childbearing age (15-49 years) must have a negative pregnancy test within 7 days before starting treatment;
• PT or INR \<1.5 ULN, and APTT \<1.5 ULN；
• Expect to live at least 12 weeks；

You may not qualify if:

• Received any antineoplastic therapy within 2 weeks prior to initial treatment；
• Systemic diseases that have not been stably controlled after treatment, such as diabetes, serious organic cardiovascular and cerebrovascular diseases, cardiac insufficiency, hypertension, heart block above ⅱ degree, myocardial infarction within 6 months, cerebral infarction within 6 months, etc.
• Pregnancy or lactation;
• Uncontrolled infectious diseases, such as baseline HBV DNA≥2000 IU/ml, anti-HIV positive, HCV-RNA positive;
• Other active infections of significant clinical significance;
• Subjects with other active malignancies within the past 5 years, such as basal or squamous skin cancer, superficial bladder cancer, or breast cancer in situ, that have been completely cured and do not require follow-up treatment are excluded;
• Severe autoimmune diseases such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, or Wegener's granuloma require long-term (more than 2 months) systemic immunosuppressive therapy, but subjects with the following conditions are admitted:
• Autoimmune hypothyroidism requiring only hormone replacement therapy; Skin disorders that do not require systemic treatment (e.g., eczema, a rash of less than 10% of the body surface);
• Subjects with allergic constitution, allergy to immunotherapy or related drugs;
• Organ failure; Coronary heart: grades ⅲ and ⅳ;Or hypertension that cannot be controlled by standard treatment, a history of myocarditis or myocardial infarction within one year; Gallo liver: achieves grade C on the Child-Turcotte-Pugh liver function scale; Gallonic kidney: renal failure and uremia; Lung: symptoms of severe respiratory failure; Brain unconsciously: people with consciousness disorder have active brain metastases;
• Patients with active bleeding and thrombotic diseases requiring treatment;
• Patients with uncontrollable pleural and abdominal effusion requiring clinical treatment or intervention;
• Subjects requiring systemic corticosteroids (equivalent to \>10 mg prednisone/day) within 14 days prior to enrollment or during the study period;
• The following conditions are allowed to join the group:
• Allow subjects to use topical or inhaled corticosteroids; Allows short-term (≤7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune allergic diseases;

Sponsors & Collaborators

• Shanghai Fengxian District Central Hospital: lead
• Shanghai Yuansong Biotechnology Co., LTD: collaborator

Study Sites (1)

Shanghai Fengxian District Central Hospital

Shanghai, Shanghai Municipality, 201406, China

RECRUITING

Related Publications (1)

• He Y, Huang X, Li X, Liu H, Liu M, Tao J, Shan Y, Raza HK, Liu Y, Zhong W, Cao XP, Yang YY, Li R, Fang XL, Zhang KJ, Zhang R, Liu F. Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial. J Immunother Cancer. 2024 May 7;12(5):e008999. doi: 10.1136/jitc-2024-008999.

  PMID: 38719544 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Melanoma; Breast Neoplasms; Urinary Bladder Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Lung Neoplasms; Virus Diseases

Interventions

Oncolytic Virotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Rong Zhang, MD

  Shanghai Fengxian District Central Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rong Zhang, MD

CONTACT

86-13818868345; rongzhang@163.com

Feng Liu, PhD

CONTACT

86-18018821121; 13916672582@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 6, 2022
• Study Start: November 30, 2021
• Primary Completion: May 30, 2023
• Study Completion: December 31, 2023
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

CN (1)