RC48 in Combination With AK104 and Bevacizumab in OCCC (DAB)

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

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)

Study Overview

• Status: Recruiting
• Conditions: Ovary Cancer
• Intervention / Treatment: Drug: Disitamab vedotin in combination with AK104 and bevacizumab for the treatment of recurrent and persistent clear cell ovarian cancer

Detailed Description

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
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing Li, doctor; Phone Number: 15915893493; Email: lijing228@mail.sysu.edu.cn
• Study Contact Backup: Name: Miaofang Wu, doctor; Phone Number: 13828494674; Email: wmiaofang@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-Sen Memorial Hospital
      • Contact: Jing Li, doctor; Phone Number: +8615915893493; Email: lijing228@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 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	Drug: Disitamab vedotin in combination with AK104 and bevacizumab for the treatment of recurrent and 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate of advanced or recurrent ovarian clear cell carcinoma	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progress	Time to progress of advanced or recurrent ovarian clear cell carcinoma	2 years
Adverse event	Adverse event rate of treatment with RC48 in combination with AK104 and bevacizumab	2 years
The time to the first subsequent therapy	The time to the first subsequent therapy for enrolled patients	2 years
Time to response	Time to response for enrolled patients	2 years
Duration of response	Duration of response of advanced or recurrent ovarian clear cell carcinoma	2 years
Disease control rate	Disease control rate of patients with recurrent or advanced ovarian clear cell carcinoma receiving intervention	2 years
Progression free survival	Progression free survival of enrolled patients with recurrent or advanced ovarian clear cell	2 years
Overall survival	Overall survival of enrolled patients with recurrent or advanced ovarian clear cell	2 years
Eastern Cooperative oncology group performance status score	ECOG score of enrolled patients	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker	Explore biomarkers for predicting the response of OCCC to combination therapy, including but not limited to PD-L1, TMB, MMRd, MSI-H, HRR related genes, and lymphocyte infiltration	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: August 2, 2024
• First Submitted That Met QC Criteria: August 2, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: bevacizumab; AK104; Disitamab vedotin
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immunoconjugates; Bevacizumab; Disitamab vedotin
• Other Study ID Numbers: SYSKY-2024-532-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Don't share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No