794TiP - Disitamab vedotin and zimberelimab combined with stereotactic body radiation therapy for the treatment of recurrent, metastatic cervical cancer: A single-arm, open-label, phase II study

Background

Despite advancements in the last 2 decades, patients(pts) with recurrent or metastatic cervical cancer (R/M CC) continue to have poor prognoses and limited treatment options.Novel therapies and targets are needed. Zimberelimab is a PD-1 monoclonal antibody and has been approved by the NMPA for the treatment of pts with R/M CC. However, the efficacy of immune checkpoint inhibitors (ICIs) mono-therapy tends to be limited. Disitamab Vedotin, a HER2-targeting antibody-drug conjugate (ADC), has demonstrated manageable safety profile and positive efficacy in HER2-expressing R/M CC. Disitamab Vedotin in combination with PD-1 immunotherapy has shown remarkable results in locally advanced or metastatic urothelial carcinoma, indicative of a synergistic effect between HER2-ADC and PD-1 immunotherapy. Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response, which is complementary to PD-1 immunotherapy. In this study, we aim to conduct a prospective phase II trial to investigate the efficacy and safety of Disitamab Vedotin plus Zimberelimab combined with SBRT in patients with R/M CC.

Trial design

This phase II, single-arm, open-label study uses a Simon two-stage design and aimes to enroll 40 patients. Part 1 of the study will evaluate the safety and tolerability of Disitamab Vedotin plus Zimberelimab combined with SBRT.Recommended dose(RD) of Disitamab Vedotin will be confirmed. Part 2 of the study is to evaluate the anti-tumor activity of the combination. SBRT combination therapy includes 1 cycle of Disitamab Vedotin (RD,Q2W) and Zimberelimab (240mg,Q2W) on day 1 followed by SBRT on day 2. Maintenance treatment includes injection of Disitamab Vedotin(RD,Q2W) and Zimberelimab (240mg,Q2W) on day 1 of each 2-week cycle and the duration of the treatment will be up to 24 months. Patients will continue the treatment until they experience disease progression or unacceptable toxicity. Primary endpoints: objective response rate. Secondary endpoints: progression free survival, overall survival, disease control rate,during of response,time to response,time to progression.

Clinical trial identification

ChiCTR2300072129.

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

RemeGen Co., Ltd.

Disclosure

The author has declared no conflicts of interest.