The Application of Novel Oncolytic Virus in Late Stage Solid Tumors

NCT06080984 | Unknown Phase 1

• 1 other identifier: 2023-833
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of novel oncolytic virus in late stage solid tumors.

Conditions

Malignant Tumor

Keywords

Solid Tumors; Oncolytic Virus

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Adverse events defined as the number of participants with adverse events

  up to 12 months

Secondary Outcomes (3)

• Objective response rate

  up to 12 months

• Progress-Free Survival

  up to 12 months

• Overall Survival

  up to 12 months

Study Arms (3)

Treatment Cohort 1

EXPERIMENTAL

This arm includes 6 head and neck squamous cell carcinoma patients. Patients in the study receive intratumoral treatment with a novel oncolytic virus SDJ001 at two dose levels: 5x10\^11 and 1x10\^12 pfu per person. At the current dose levels, intratumoral injection is administered on the first day of each treatment cycle. Each treatment cycle consists of three weeks, continuing until tumor growth is observed following injection or until the patient experiences intolerable toxic effects. Ultrasound-guided injection may be used when necessary (2.0 mL for tumors with a diameter \>2.5 cm, 1.0 mL for diameters of 1.5-2.5 cm, 0.5 mL for diameters of 0.5-1.5 cm, and 0.1 mL for diameters \<0.5 cm, with a maximum of 4 mL).

Drug: Oncolytic Virus SDJ001

Treatment Cohort 2

EXPERIMENTAL

This arm includes 9 melanoma patients. Patients in the study receive intratumoral treatment with a novel oncolytic virus YD06-1 at a concentration of 10\^6 pfu/mL to 10\^8 pfu/ml following a dose escalation plan. Each subject receives only one injection at the corresponding concentration, with the dose determined based on the size of the tumor mass. (Diameter ≤1.5 cm, maximum of 1 mL; diameter 1.5-2.5 cm, maximum of 2 mL; diameter greater than 2.5 cm, maximum of 4 mL). The second dose is administered three weeks after the first dose, followed by subsequent doses at two-week intervals.

Drug: Oncolytic Virus YD06-1

Treatment Cohort 3

EXPERIMENTAL

This arm includes 9 sarcoma patients. Patients in the study receive intratumoral treatment with a novel oncolytic virus YD06-1 at a concentration of 10\^6 pfu/mL to 10\^8 pfu/ml following a dose escalation plan. Each subject receives only one injection at the corresponding concentration, with the dose determined based on the size of the tumor mass. (Diameter ≤1.5 cm, maximum of 1 mL; diameter 1.5-2.5 cm, maximum of 2 mL; diameter greater than 2.5 cm, maximum of 4 mL). The second dose is administered three weeks after the first dose, followed by subsequent doses at two-week intervals.

Drug: Oncolytic Virus YD06-1

Interventions

Oncolytic Virus SDJ001 DRUG

Patients in the study receive intratumoral treatment with SDJ001 at two dose levels: 5x10\^11 and 1x10\^12 pfu per person. At the current dose levels, intratumoral injection is administered on the first day of each treatment cycle. Each treatment cycle consists of three weeks, continuing until tumor growth is observed following injection or until the patient experiences intolerable toxic effects. Ultrasound-guided injection may be used when necessary (2.0 mL for tumors with a diameter \>2.5 cm, 1.0 mL for diameters of 1.5-2.5 cm, 0.5 mL for diameters of 0.5-1.5 cm, and 0.1 mL for diameters \<0.5 cm, with a maximum of 4 mL).

Treatment Cohort 1

Oncolytic Virus YD06-1 DRUG

Patients in the study receive intratumoral treatment with a novel oncolytic virus YD06-1 at a concentration of 10\^6 pfu/mL to 10\^8 pfu/ml following a dose escalation plan. Each subject receives only one injection at the corresponding concentration, with the dose determined based on the size of the tumor mass. (Diameter ≤1.5 cm, maximum of 1 mL; diameter 1.5-2.5 cm, maximum of 2 mL; diameter greater than 2.5 cm, maximum of 4 mL). The second dose is administered three weeks after the first dose, followed by subsequent doses at two-week intervals.

Treatment Cohort 2; Treatment Cohort 3

Eligibility Criteria

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

You may qualify if:

• Male or female patients: ≥18 years.
• a)Patients with confirmed advanced squamous cell carcinoma of the head and neck (including nasopharynx) who meet the following criteria: Patients who have failed standard second-line treatment. Tumors that cannot be cured through local treatment (surgery or definitive radiation therapy).
• b)Patients with stage III malignant melanoma who are not eligible for surgical resection, or patients with stage IV malignant melanoma, who have failed at least two lines of standard treatment (including chemotherapy, immunotherapy or targeted therapy).
• c)Patients with locally unresectable or metastatic advanced soft tissue sarcomas, who have failed prior systemic treatments.
• ECOG performance status score: 0-1.
• Expected survival ≥3 months.
• Time since the last chemotherapy/radiotherapy/surgery is more than 28 days.
• Adequate organ function, as defined by the following criteria within 14 days before enrollment:
• Hematology: Hemoglobin ≥90g/L (without blood transfusion in the last 14 days); Neutrophil count \>1.5×10\^9/L; Platelet count ≥80×10\^9/L.
• Biochemistry: Total bilirubin ≤1.5×ULN (upper limit of normal); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; if there is liver metastasis, ALT or AST ≤5×ULN; Estimated glomerular filtration rate ≥60ml/min (Cockcroft-Gault formula).
• Cardiac Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%.
• Patients with injectable lesions (those suitable for direct injection or injection with the assistance of medical imaging), defined as follows: at least one injectable lesion in the skin, mucous membrane, subcutaneous tissue, or lymph node with a longest diameter ≥10 mm, or multiple injectable lesions with a total longest diameter ≥10 mm
• No continuing acute toxic effects of any prior radiotherapy, chemotherapy, or surgical intervention, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Grade 1.
• Signed written informed consent Subjects must sign a written informed consent form approved by the competent authority and the research institution and date it. The informed consent form must be signed before any protocol-related procedures (not part of the subject's routine medical care) are conducted.
• Subjects must be willing and able to comply with the scheduled visits, treatment regimen, laboratory tests, and other requirements of the study.

You may not qualify if:

• Participated in another drug clinical trial within the past 4 weeks.
• Tumor located near major blood vessels or the trachea.
• Has poorly controlled clinical heart symptoms or diseases, such as NYHA class 2 or higher heart failure, unstable angina, myocardial infarction within the past year, clinically significant ventricular or supraventricular arrhythmias requiring treatment or intervention.
• For female subjects: pregnant or lactating women.
• Persistent or active infections, including but not limited to: active pulmonary tuberculosis, positive HIV (Human Immunodeficiency Virus) antibodies, positive HBsAg (Hepatitis B Surface Antigen), positive HBcAb (Hepatitis B Core Antibody), and positive HCV (Hepatitis C Virus) antibody test results.
• Participants who are positive for HBsAg and/or HBcAb must also provide baseline HBV DNA results and undergo HBV DNA monitoring during the treatment according to the protocol.
• Participants with HBV DNA results of 10\^4 copies/ml or ≥ 2000 IU/mL and any of the following conditions should be excluded: 1) positive results for HBsAg and/or HBeAg; 2) positive results for HBcAb and negative results for all others.
• Patients with a positive HCV antibody test result are only ineligible for study participation if their HCV RNA test result is positive..
• Has a history of substance abuse that cannot be discontinued or has psychiatric disorders.
• Has any active autoimmune disease or a history of autoimmune disease, including but not limited to uveitis, enteritis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or childhood asthma that has completely resolved in adulthood without the need for intervention may be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included.
• Patients who have used systemic corticosteroids (\>10g/day of prednisone or an equivalent dose) or other immunosuppressive drugs in the 4 weeks prior to the initial administration of the study drug will be excluded.
• Has a history of substance abuse or known medical, psychological, or social conditions, such as a history of alcoholism or drug abuse.
• Known allergy, hypersensitivity reaction, or intolerance to oncolytic virus research (including any excipients). A history of severe allergies to any drugs, foods, or vaccines, such as anaphylactic shock, angioedema, respiratory distress, purpura, thrombocytopenic purpura, or localized allergic necrotizing reaction (Arthus reaction), etc.
• Female subjects with pregnancy plans during the screening period or male subjects with partners who have pregnancy plans.
• Has accompanying diseases judged by the investigator to be seriously harmful to patient safety or affecting the patient's completion of the study.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (9)

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Ibarra AMC, Cecatto RB, Motta LJ, Dos Santos Franco AL, de Fatima Teixeira da Silva D, Nunes FD, Hamblin MR, Rodrigues MFSD. Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers. Lasers Med Sci. 2022 Apr;37(3):1441-1470. doi: 10.1007/s10103-021-03462-3. Epub 2021 Dec 2.

  PMID: 34855034 BACKGROUND

• Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

  PMID: 26014293 BACKGROUND

• Chesney JA, Ribas A, Long GV, Kirkwood JM, Dummer R, Puzanov I, Hoeller C, Gajewski TF, Gutzmer R, Rutkowski P, Demidov L, Arenberger P, Shin SJ, Ferrucci PF, Haydon A, Hyngstrom J, van Thienen JV, Haferkamp S, Guilera JM, Rapoport BL, VanderWalde A, Diede SJ, Anderson JR, Treichel S, Chan EL, Bhatta S, Gansert J, Hodi FS, Gogas H. Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. J Clin Oncol. 2023 Jan 20;41(3):528-540. doi: 10.1200/JCO.22.00343. Epub 2022 Aug 23.

  PMID: 35998300 BACKGROUND

• Harrington KJ, Kong A, Mach N, Chesney JA, Fernandez BC, Rischin D, Cohen EEW, Radcliffe HS, Gumuscu B, Cheng J, Snyder W, Siu LL. Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clin Cancer Res. 2020 Oct 1;26(19):5153-5161. doi: 10.1158/1078-0432.CCR-20-1170. Epub 2020 Jul 15.

  PMID: 32669371 BACKGROUND

• Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC, Nelson BH. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer. 2018 Jul;18(7):419-432. doi: 10.1038/s41568-018-0009-4.

  PMID: 29695749 BACKGROUND

• Xia ZJ, Chang JH, Zhang L, Jiang WQ, Guan ZZ, Liu JW, Zhang Y, Hu XH, Wu GH, Wang HQ, Chen ZC, Chen JC, Zhou QH, Lu JW, Fan QX, Huang JJ, Zheng X. [Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus]. Ai Zheng. 2004 Dec;23(12):1666-70. Chinese.

  PMID: 15601557 BACKGROUND

• Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2018 Aug 9;174(4):1031-1032. doi: 10.1016/j.cell.2018.07.035. No abstract available.

  PMID: 30096300 BACKGROUND

• Goradel NH, Baker AT, Arashkia A, Ebrahimi N, Ghorghanlu S, Negahdari B. Oncolytic virotherapy: Challenges and solutions. Curr Probl Cancer. 2021 Feb;45(1):100639. doi: 10.1016/j.currproblcancer.2020.100639. Epub 2020 Aug 15.

  PMID: 32828575 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Study Officials

• Xingchen Peng

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng

CONTACT

+86 18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: October 12, 2023
• Study Start: October 15, 2023
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2025
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)