The Safety, Tolerability, and Efficacy of KD01 in Gynecologic Malignancies

Recombinant oncolytic adenovirus injection (KD01)is an oncolytic vius product. Its main component is a conditionally replicativerecombinant human type 5 adenovirus, where part of the E3 region has been replaced with the gene encoding the tBid apoptoticprotein.AK104 is a humanized bispecific antibody co-targeting PD-1 (Programmed Cell Death Protein 1) and CTLA-4 (Cytotoxic T-Lymphocyte-Associated Antigen 4)-two key immune checkpoint receptors. It is designed as a novel tetrameric construct that preferentially binds to tumor-infiltrating lymphocytes (TILs) co-expressing PD-1 and CTLA-4 in the tumor microenvironment (withhigher avidity than in peripheral tissues).This study aims to investigate the therapeutic efficacy and safety of recombinant oncolytic adenovirus (KD01) in patients with gynecologic malignancies. Meanwhile, it will explore the impact of KD01 on the immune function of cervical cancer patients as well as its tumor cell-killing mechanism. This research is expected to provide novel strategies and approaches for the treatment of gynecologic malignancies, and contribute to improving the rehabilitation and quality of life of patients. The study is divided into Phase I and Phase II. Phase II consists of Cohort A (cervical cancer cohort) and Cohort B (endometrial cancer cohort).Phase I will include patients with gynecologic malignancies who have failed systemic therapy.Phase II will include reproductive-aged women with a strong desire to preserve fertility.Phase II Cohort A will include patients with cervical squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, staged as IB1 (tumor size ≥1 cm), IB2, IB3 (tumor size ≤5 cm) and IIA1 (based on FIGO 2018 staging system); baseline MRI examination confirms that the lesion does not involve the lower uterine segment; for patients in Stage II , the length of vaginal involvement is \< 2 cm.Phase II Cohort B will include patients with endometrial atypical hyperplasia or endometrial adenocarcinoma (FIGO Grade 1-Grade 2, FIGO 2023 Stage IA1 and IA2), with mismatch repair deficiency (MMRd) or no response to progestogen therapy; baseline MRI examination combined with chest CT or PET/CT confirms that the lesion is limited to the endometrial layer or superficial myometrium, without obvious involvement of the deep myometrium, cervix or extrauterine sites.