Exploratory Study on the Safety and Efficacy of Disitamab Vedotin in Combination with Anlotinib Hydrochloride for the Treatment of HER-2-expressing Recurrent Platinum-resistant Ovarian Cancer.

Summary

Ovarian cancer is one of the three major malignant tumors of the female reproductive system. Even if newly diagnosed ovarian cancer patients undergo ideal tumor cell reduction surgery and postoperative chemotherapy, 70% to 80% of ovarian cancer patients still experience recurrence. According to the length of PFI (platinum free interval), recurrent ovarian cancer (ROC) can be classified into platinum resistant ROC (\<6 months) and platinum sensitive ROC (\>6 months). There is currently no optimal treatment plan for platinum resistant ovarian cancer (PROC), and the prognosis for patients is poor. The guidelines recommend non platinum monotherapy chemotherapy for patients with PROC, but non platinum monotherapy has a low objective response rate (ORR) (\<20%), progression free survival (PFS) (\<4 months), and overall survival (OS,\<12 months), with significant adverse reactions and affecting quality of life. Therefore, PROC patients urgently need new and better treatment options.

Antibody conjugated drugs (ADCs) have made breakthrough therapeutic progress in multiple tumor types, and currently ADCs have been approved by the FDA for the treatment of cervical cancer and ovarian cancer. HER2 (Human Epidermal Growth Factor Receptor 2) is a member of the epidermal growth factor receptor (EGFR) family, also known as the tyrosine protein kinase receptor. Research has shown that HER2 expression is associated with poor prognosis in ovarian cancer, and patients with HER2 positive expression have a worse prognosis. Vidiximab (RC48) is a novel HER2 antibody conjugate drug that received Breakthrough Therapy Design from the US Food and Drug Administration (FDA) in April 2020. Preclinical studies of ovarian cancer have shown that vediximab exhibits effective cytotoxicity against HER2 expressing ovarian tumor cell lines. Meanwhile, the registration study of RC48 for gynecological tumors is underway, and its latest data was reported at the 2024 European Congress of Gynecological Oncology (ESGO), which showed that in patients with recurrent or metastatic cervical cancer, the ORR of RC48 monotherapy was 36.4%, the median PFS was 4.37 months, and the 1-year OS was 66%. Compared to other chemotherapy drugs, it also has significant advantages in terms of toxic side effects, with severity mostly ranging from grade 1-2. Symptomatic treatment can achieve complete recovery or relief.

Anti angiogenic drugs, including anti vascular endothelial growth factor (VEGF) antibodies and multi-target tyrosine kinase inhibitors (TKIs), are considered potential targets for treating platinum resistant/refractory ovarian diseases . Anlotinib is a novel oral multi-target tyrosine kinase inhibitor (TKIs) . Monotherapy for PROC has achieved initial efficacy, with an ORR of 31.2%, a median PFS of 5.3 months, and a 12-month OS rate of 90.9%. In terms of safety, most of the toxic side effects are grade 1-2.

Good progress has been made in preclinical and clinical trials of ADC in combination with other anti-cancer drugs, including chemotherapy, molecular targeted drugs, anti angiogenic drugs, and immunotherapy. Among them, anti angiogenic drugs may promote the penetration and exposure of ADC to tumor cells, playing a mutually reinforcing role. Research on the combination of RC48 and anlotinib is also actively underway in other tumor types.

In summary, this study creatively conducted exploratory research in clinical PROC patients based on the different expression levels of the molecular target HER2, and adopted targeted medication according to the molecular target. At the same time, in terms of combination therapy, low toxicity and high efficiency, different toxic side reaction spectra, different mechanisms of action, and synergistic effects of dual anti-tumor drugs were selected for combination therapy. Based on the above evidence, an exploratory study was conducted on the safety and efficacy of vediximab combined with anlotinib in the treatment of HER-2 expressing recurrent platinum resistant ovarian cancer, aiming to explore the efficacy of vediximab combined with anlotinib in PROC patients, in order to further improve the remission rate and quality of life of patients while prolonging their survival.

Conditions

• Ovarian Cancer Recurrent

Interventions

DRUG

Disitamab Vedotin in Combination With Anlotinib Hydrochloride

The dose of Disitamab Vedotin(RC48) is 2.0 mg/kg iv q2w d1; The dose of Anlotinib Hydrochloride Capsules is 10mg po qd (recommended to be taken before meals and at the same time every day), taken orally continuously for 2 weeks and stopped for 1 week, with a treatment cycle of 21 days. Main research endpoint: Objective response rate (ORR) Secondary study endpoint: 1. Progression free survival (PFS) 2. Overall survival (OS) 3. Disease Control Rate (DCR) 4. Objective Duration of Response (DoR)

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-10-15

Primary Completion

2025-09-01

Completion

2025-10-15

Countries

• China

Study Locations