A Real-World Observational Study of Intratumoral H101 Oncolytic Adenovirus Combined With Immune Checkpoint Inhibitors for Advanced Metastatic Breast Cancer

NCT07850869 | Recruiting DMC

• 1 other identifier: CYEC-LCYJ-2026076-PJ-20260817
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-center, open-label, real-world observational study plans to enroll 10-15 patients with advanced (Stage IV) breast cancer who have failed multiple prior therapies \[aged 18-75, Eastern Cooperative Oncology Group Performance Status Clinical Classification（ECOG） 0-2, with measurable and injectable lesions\]. It aims to preliminarily evaluate the antitumor activity, safety, and immune-microenvironment modulation of intratumoral H101（Recombinant Human Adenovirus Type 5 Injection） oncolytic virus combined with immune checkpoint inhibitors (ICIs) in real-world practice. The regimen is determined by physicians based on clinical status and multidisciplinary input, but follows a standardized framework: 2- to 3-week cycles; H101 injected on day 1 (dose stratified by lesion size), with ICI infusion started 7±2 days later, for 4 planned cycles. Paired tumor biopsies (when feasible) and peripheral blood are collected at baseline and after 4 cycles for single-cell RNA sequencing and immune profiling, focusing on changes in T lymphocyte (T), Natural Killer cell (NK), dendritic, and macrophage subsets and correlating with clinical outcomes. Primary endpoints include adverse events (Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0（CTCAE v5.0）), objective response and local control rates (Response Evaluation Criteria in Solid Tumors Version 1.1（RECIST 1.1）), 4-cycle completion, and toxicity-related discontinuation. Secondary endpoints include disease control rate, progression-free survival (Kaplan-Meier), and dynamic immune changes. First radiological assessment occurs at 6-8 weeks post-treatment, then every 3 months until progression, loss to follow-up, or 1 year. If re-biopsy is unsafe, only peripheral blood may be collected without protocol violation. Comprehensive follow-up, data confidentiality, and missing-data handling are in place to ensure scientific validity and participant protection.

Conditions

Breast Cancer (Locally Advanced or Metastatic)

Keywords

H101 oncolytic virus; immune checkpoint inhibitors; advanced metastatic breast cancer; tumor immune microenvironment; intratumoral injection

Outcome Measures

Primary Outcomes (5)

• Incidence of Adverse Events

  Metric/method of measurement : Common Terminology Criteria for Adverse Events version 5.0

  From first dose of study treatment through 30 days after the last dose (up to approximately 8-12 weeks)

• Objective Response Rate

  Response Evaluation Criteria in Solid Tumors version 1.1

  6-8 weeks after the end of treatment (after completion of 4 treatment cycles)

• Local Control Rate

  According to clinical and radiological assessment

  Baseline and every 3 months up to 1 year after the end of treatment

• Treatment Feasibility

  Measured by completion rate and adherence rate

  During the treatment period (up to 4 cycles, each cycle 2-3 weeks)

• Tolerability of the study drug in participants

  Tolerability will be assessed by the incidence, severity, and relatedness of TEAEs, and the proportion of participants who discontinue treatment due to TEAEs.

  From first dose of study treatment through 30 days after the last dose (up to approximately 8-12 weeks)

Secondary Outcomes (2)

• Disease Control Rate

  Baseline and up to approximately 6 months (including 6-8 weeks after the end of treatment)

• Progression-Free Survival

  From first dose of study treatment until disease progression per RECIST v1.1 or death from any cause, whichever occurs first (up to approximately 2 years)

Study Arms (1)

Treatment group

H101 (Recombinant Human Adenovirus Type 5 Injection)+Anti-Programmed Cell Death Protein 1 Antibody（Anti-PD-1 antibody） ± Anti-Cytotoxic T-Lymphocyte-Associated Protein 4 Antibody（anti-CTLA-4 antibody） H101 (Recombinant Human Adenovirus Type 5 Injection) Route of administration: Intratumoral injection Dose: Stratified dosing according to lesion size, using the dose specified in the package insert and the dose based on prior clinical experience (multipoint injection) Frequency: Once per cycle Treatment course: 2-3 weeks per cycle, for a total of 4 cycles Anti-PD-1 antibody ± anti-CTLA-4 antibody Initiation time: 7 ± 2 days after the first H101 injection Administration schedule: Once per cycle

Eligibility Criteria

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

Study Population

This study will enroll 15 patients with advanced metastatic breast cancer presenting with multiple metastases, who have failed multiple prior lines of systemic therapy, and are aged 18 to 75 years. Subjects will be primarily recruited from the patient population at Foshan Fosun Chancheng Hospital. All eligible subjects must meet all inclusion criteria and none of the exclusion criteria.

You may qualify if:

• Age 18 to 75 years, both genders;
• Pathologically confirmed breast cancer (Stage IV)；
• Disease progression after at least one line of standard systemic therapy；
• ECOG performance status 0-2；
• Intolerant to or refusal of standard chemotherapy；
• At least one radiologically measurable lesion per RECIST 1.1 criteria；
• At least one lesion amenable to puncture/injection (i.e., accessible for intratumoral injection)；
• Estimated life expectancy ≥3 months；
• Adequate major organ function as defined by the following laboratory values:Absolute neutrophil count (ANC) ≥1.5×10⁹/L,Platelet count (PLT) ≥100×10⁹/L,Hemoglobin (Hb) ≥90 g/L,Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN),Serum creatinine (Cr) ≤1.5× ULN；
• Signed informed consent form；
• Agreement to provide tumor tissue samples and peripheral blood samples before and after treatment for research purposes.。

You may not qualify if:

• Known allergy to H101 formulation, PD-1 inhibitors, or any of their excipients ;
• Lymphocyte count \<0.5×10⁹/L;
• Severe infection, active infection (particularly HBV, HCV, HIV), or severely immunocompromised status;
• Presence of lesions that cannot be safely punctured/injected;
• Prior treatment with PD-1/PD-L1 inhibitors with grade ≥3 immune-related adverse events that have not resolved;
• Concurrent active malignancy other than breast cancer (except for those cured for \>5 years with no evidence of recurrence);
• Uncontrolled brain metastases;
• Pregnant or breastfeeding wome;
• Psychiatric disorders, cognitive impairment, or poor compliance that may interfere with study participation and completion;
• Severe cardiac, hepatic, or renal failure;
• Long-term immunosuppressive therapy;
• Uncontrolled active autoimmune disease.

Sponsors & Collaborators

• Jie Yuan，MD: lead

Study Sites (1)

Foshan Fosun Chancheng Hospital

Guangdong, Foshan, China

RECRUITING

Related Publications (6)

• Lin J, Lin Z, Zhang H, et al.Recombinant human adenovirus type 5 (H101) combined with anti-PD-1 monoclonal antibody in patients with advanced melanoma after immunotherapy failure.J Clin Oncol. 2025 ASCO Annual Meeting Abstract.DOI：10.1200/JCO.2025.43.16_suppl.e21505.

  BACKGROUND

• Zhang J, Zhang Q, Liu Z, Wang J, Shi F, Su J, Wang T, Wang F. Efficacy and Safety of Recombinant Human Adenovirus Type 5 (H101) in Persistent, Recurrent, or Metastatic Gynecologic Malignancies: A Retrospective Study. Front Oncol. 2022 Apr 28;12:877155. doi: 10.3389/fonc.2022.877155. eCollection 2022.

  PMID: 35574359 BACKGROUND

• Zhang Q, Zhang J, Liu Z, Wang J, Wang F, Wang T, Shi F, Su J, Zhao Y. Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy. Drug Des Devel Ther. 2023 Nov 27;17:3507-3522. doi: 10.2147/DDDT.S429180. eCollection 2023.

  PMID: 38046281 BACKGROUND

• Zhao Q, Xiao M, Ma J, Fu C, Gao Q, Bi Y. Reverse resistance to immune checkpoint inhibitor in a patient with recurrent cardia cancer by intratumoral injection of recombinant human adenovirus type 5: a case report and literature review. Front Oncol. 2024 Nov 11;14:1465664. doi: 10.3389/fonc.2024.1465664. eCollection 2024.

  PMID: 39588306 BACKGROUND

• Duan C, Liu X. Recombinant human adenovirus type 5 administration for the treatment of malignant ascites or pleural effusion in cancer patients: a meta-analysis. Front Oncol. 2025 Sep 17;15:1592995. doi: 10.3389/fonc.2025.1592995. eCollection 2025.

  PMID: 41040530 BACKGROUND

• Wang ZM, Li MK, Yang QL, Duan SX, Lou XY, Yang XY, Liu Y, Zhong YW, Qiao Y, Wang ZS, Sun L, Qian F. Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells. Acta Pharmacol Sin. 2024 Dec;45(12):2646-2656. doi: 10.1038/s41401-024-01349-x. Epub 2024 Jul 19.

  PMID: 39030309 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue . Peripheral blood sample

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jie Yuan, Doctoral degree

CONTACT

+86 13016007353; candlewjy@163.com

Jie Yuan

CONTACT

0757-82778323

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 30, 2026
• Study Start: September 9, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)