The efficacy of recombinant human adenovirus type 5 (H101) intra-tumor therapy in persistent/recurrent/metastatic gynecological cancer and the exploration of changes in tumor microenvironment.

person Qiying Zhang Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China info_outline Qiying Zhang, Zi Liu, Jing Zhang, Fei Wang, Shi Fan, Juan Wang, Tao Wang, Jin Su

Authors person Qiying Zhang Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China info_outline Qiying Zhang, Zi Liu, Jing Zhang, Fei Wang, Shi Fan, Juan Wang, Tao Wang, Jin Su Organizations Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China Abstract Disclosures Research Funding No funding sources reported Background: Previous small sample retrospective study has showed that H101 has promising efficacy and favorable safety in patients with persistent /recurrent/metastatic (P/R/M) gynecological cancer. To further assess the effecacy and safety of H101 in P/R/M gynecological cancer, we conducted this prospective Phase II study and further explore the tumor microenvironment (TME) through Cell DIVE multiplexed imaging solution. Methods: This was a prospective, open-label, single-arm study (clinicaltrials.gov number NCT05051696). P/R/M gynecological cancer patients who had at least one injectable lesion and had received at least one line of systemic therapy or could not tolerate chemotherapy were eligible. H101 (0.5-1.5×10 12 viral particles) was injected into the target lesion once a day for 5 consecutive days, with a cycle of 3 weeks and a maximum of 4 cycles. Whether added other medications was at the physician’s discretion. Cell DIVE multiplexing of 15 immune cell markers were performed in 6 paired pre- and post-H101 injected tumors. Results: From September 2021 to February 2024, 116 P/R/M patients received H101 intro-tumor injection, of which 16 patients did not evaluate for the efficacy endpoint. At the data cut-off of February 2024 for the primary analysis, overall median follow-up time was 10 months. The best complete response was achieved in 30 patients, 34 patients achieved partial response and 15 patients had stable disease, yielding an objective response rate of 64%. The disease control rate was 79% by RECIST1.1, and the median duration of time was 7.1 months. The median progression-free survival was 8.7 months, and the median overall survival was currently not reached. Furthermore, 83% of the patients experienced treatment-related adverse events and the major adverse events were fever (64%), fatigue (31%) and pain at the injection site (25%). Compared with baseline, the number of B cells, T regulatory cells and Ki 67+ tumor cells decreased in the injected lesions, while the number of M1 macrophage, monocytes, CD4 and CD8 T cells were increased. Additionally, B cells and CD68+CD163- tumor associated macrophage (M1 TAM) were higher in response patients. Conclusions: This was the first reported large sample size prospective study regarding H101 in gynecological cancer. These results indicated that H101 as second line or later therapy for P/R/M gynecological cancer patients was efficacious and safe. Cell DIVE multiplexing of immune cell markers suggested that the H101 efficiently reshaped the TME and the response of H101 oncolytic virotherapy may associated with increased B cells and M1 TAM in the TME. Clinical trial information: NCT05051696.

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