Disitamab vedotin (RC48) with AK104 and bevacizumab for recurrent or persistent clear cell ovarian cancer
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
This trial tests whether combining a HER2-targeted antibody–drug conjugate (disitamab vedotin) with the PD-1/CTLA-4 bispecific AK104 and bevacizumab helps people with recurrent or persistent ovarian clear cell carcinoma.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 39 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | Female |
| Sponsor | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Academic / other |
| Drugs / interventions | bevacizumab, CAR-T, chemotherapy, immunotherapy, Disitamab, vedolizumab |
| Locations | 1 site (Guanzhou, Guangdong) |
| Trial ID | NCT06540729 on ClinicalTrials.gov |
What this trial studies
This is a single-arm, phase II multicenter trial of disitamab vedotin (RC48) combined with AK104 and bevacizumab in patients with recurrent or persistent ovarian clear cell carcinoma. The rationale is that anti-angiogenic therapy and immune checkpoint modulation may synergize in this tumor type and that HER2-directed ADCs can both directly kill tumor cells and modulate anti-tumor immunity. Key eligibility includes pathologically confirmed OCCC (≥70% clear cell if mixed), HER2 IHC ≥1+, at least one measurable lesion by RECIST 1.1, and up to two prior lines of chemotherapy. The study will administer the three-drug combination and measure anti-tumor activity and safety outcomes including response rate and adverse events.
Who should consider this trial
Good fit: Adults with recurrent or persistent ovarian clear cell carcinoma, HER2 IHC ≥1+, at least one measurable lesion per RECIST 1.1, and who have received no more than two prior lines of chemotherapy are ideal candidates.
Not a fit: Patients with no HER2 expression (IHC 0), who have had more than two prior chemotherapy regimens, or who cannot tolerate immunotherapy or anti-angiogenic therapy are less likely to benefit.
Why it matters
Potential benefit: If successful, the combination could produce higher tumor response rates and extend survival for patients with recurrent or persistent ovarian clear cell carcinoma compared with current options.
How similar studies have performed: Prior studies have shown activity for HER2-targeted ADCs in ovarian cancer and promise for combining anti-angiogenesis with immunotherapy, but the three-way combination in OCCC is novel and not yet widely tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * The pathological diagnosis confirms ovarian clear cell carcinoma. In cases of mixed carcinoma, a prerequisite is that clear cell carcinoma constitutes at least 70% of the tumor mass. Moreover, adherence to RECIST 1.1 criteria mandates the presence of at least one evaluable lesion. * HER2 IHC ≥1+. * Treatment-naïve individuals encompass those experiencing tumor progression during postoperative chemotherapy and those who, following platinum-containing neoadjuvant chemotherapy, have not undergone surgical intervention yet and subsequently manifested progression during or after platinum-containing chemotherapy, provided that they have received a maximum of 2 prior lines of chemotherapy. * Recurrent patients, whether platinum-sensitive or platinum-resistant, include those lacking a platinum-free interval of ≥6 months and who, post-recurrence, have undergone re-administration of platinum-containing chemotherapy but have demonstrated an inability to tolerate toxic reactions, with a maximum of 2 lines of chemotherapy post-recurrence. * Previous utilization of bevacizumab is permissible. * Adequate bone marrow reserve function necessitates pre-operative blood routine parameters meeting specific criteria: white blood cell count ≥3.0×10\^9/L, neutrophil count ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, and hemoglobin ≥80 g/L. * atisfactory organ function entails biochemical test results within defined limits: AST ≤2.5× upper limit of normal (ULN), ALT ≤2.5× ULN, serum total bilirubin ≤1.5× ULN, and creatinine ≤1.5× ULN. * ECOG performance status score ranging from 0 to 1. * Patient participation is contingent upon voluntary execution of an informed consent form. Exclusion Criteria: * Patients with a history of immunotherapy, including treatments targeting PD-1, PD-L1, CAR-T, and CTLA-4. * Patients diagnosed with other malignancies within the past five years, excluding skin cancer and thyroid cancer. * Patients with an expected survival of ≤12 weeks. * Patients with a known allergy to taxane-based medications. * Patients who, based on clinical assessment, have contraindications for receiving immunotherapy and/or bevacizumab, such as uncontrolled infections, gastrointestinal fistula, autoimmune diseases, active hepatitis, or active bleeding. Patients currently undergoing treatment with investigational anti-cancer drugs in other clinical trials. * Patients with any unstable condition or situation that may compromise their safety or adherence to the study protocol.
Where this trial is running
Guanzhou, Guangdong
- Sun Yat-sen Memorial Hospital — Guanzhou, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: Jing Li, doctor
- Email: lijing228@mail.sysu.edu.cn
- Phone: 15915893493
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.