Disitamab vedotin (RC48) in combination with AK104 (PD-1/CTLA-4 bispecific) and bevacizumab for the treatment of recurrent and persistent clear cell ovarian cancer: a single-arm, phase II, multicenter study (DAB OCC study)
Ovarian clear cell carcinoma (OCCC) ranks as the second most common epithelial ovarian malignancy in Asian women, characterized by extremely poor prognosis, with a median overall survival (OS) of 25.3 months. OCCC demonstrates a dismal response rate to conventional chemotherapy, and once in a state of persistence or recurrence, treatments become severely limited, with a mere 5-year survival rate of 13.2%, with over two-thirds of patients succumbing within 1 year. Thus, there is an urgent need to explore new therapeutic approaches for recurrent and persistent OCCC patients. Evidence suggests that anti-angiogenesis therapy is effective against OCCC, which tends to exhibit a "hot tumor" phenotype. Hence, the combination of anti-angiogenesis therapy with immunotherapy holds promise for recurrent and persistent OCCC. Additionally, overexpression of human epidermal growth factor receptor 2 (HER2) plays a pivotal role in OCCC resistance formation. Antibody drug conjugates (ADCs) targeting HER2 have shown increasing efficacy in ovarian cancer treatment, with significant immunomodulatory effects enhancing the efficacy of immunotherapy. Based on this evidence, the investigators hypothesize that the combination of anti-angiogenesis therapy, immunotherapy, and HER2-targeted ADCs may improve the prognosis of OCCC patients. Therefore, the investigators are initiating this clinical study aimed at evaluating the efficacy and safety of vedolizumab (HER2-targeted ADC) in combination with AK104 (anti-PD-1 and CTLA4) and bevacizumab (anti-angiogenesis) in recurrent and persistent OCCC patients (vedolizumab 2.5 mg/kg + AK104 10 mg/kg + bevacizumab 15 mg/kg, every 3 weeks), with the aim of providing new treatment options for these refractory gynecologic malignancies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Disitamab vedotin (RC48) in combination with AK104 (PD-1/CTLA-4 bispecific) and bevacizumab for the treatment of recurrent and persistent clear cell ovarian cancer
Sun Yat-sen Memorial Hospital
Guanzhou, Guangdong, China
RECRUITINGObjective Response Rate
Objective response rate of advanced or recurrent ovarian clear cell carcinoma
Time frame: 2 years
Time to progress
Time to progress of advanced or recurrent ovarian clear cell carcinoma
Time frame: 2 years
Adverse event
Adverse event rate of treatment with RC48 in combination with AK104 and bevacizumab
Time frame: 2 years
The time to the first subsequent therapy
The time to the first subsequent therapy for enrolled patients
Time frame: 2 years
Time to response
Time to response for enrolled patients
Time frame: 2 years
Duration of response
Duration of response of advanced or recurrent ovarian clear cell carcinoma
Time frame: 2 years
Disease control rate
Disease control rate of patients with recurrent or advanced ovarian clear cell carcinoma receiving intervention
Time frame: 2 years
Progression free survival
Progression free survival of enrolled patients with recurrent or advanced ovarian clear cell
Time frame: 2 years
Overall survival
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Overall survival of enrolled patients with recurrent or advanced ovarian clear cell
Time frame: 2 years
Eastern Cooperative oncology group performance status score
ECOG score of enrolled patients
Time frame: 2 years