Ipilimumab and nivolumab in patients with rare gynaecological malignancies: Results of an Australian, multi-centre, phase 2 trial (CA209-538).

Abstract

Background: Half of all gynaecological malignancies are considered rare and have limited access to evidence-based systemic treatment leading to poor outcomes. Dual immune checkpoint inhibitors (ICI) have demonstrated broad antitumour activity but have not been studied in this population. Method(s):We conducted an Australian multi-centre, phase 2 study, of combination ICI in advanced rare gynaecological cancers. Eligible patients were 18 years or older, with either a pre-treated or treatment naive, stage IV, histologically confirmed rare cancer of the female genital tract. Participants received induction ipilimumab 3 mg/kg and nivolumab 1 mg/kg every 3 weeks for four cycles, followed by maintenance nivolumab 3 mg/kg every 2 weeks or 480 mg every 4 weeks for up to two years or disease progression. The primary endpoint was disease control rate (DCR) at 12 weeks by RECIST 1.1. Secondary endpoints included the evaluation of tumour agnostic biomarkers inclusive of PD-L1 expression and tumour mutational burden (TMB). Result(s): Forty-three patients were enrolled with 10 tumour types; most (42) had received prior therapy (1-7 lines). Objective responses were observed in 12 patients (28%), and an addition seven had stable disease, corresponding to a DCR of 44%. Responses were obtained across a range of tumours including: uterine leiomyosarcoma (3/5), uterine and ovarian carcinosarcoma (3/9), ovarian clear cell (2/6), low grade serous ovarian carcinoma (1/4), vulva/vaginal SCC (1/5) and uterine serous carcinoma (1/8). No responses were observed in patients with ovarian sex cord stromal tumours (0/4). Immune-related adverse events occurred in 31 (72%) of patients with grade 3+ events in 7 (16%). Responses were higher in PD-L1 expressing tumours but were independent of TMB. Conclusion(s): Ipilimumab and nivolumab are active in a range of advanced rare gynaecological cancers with a manageable safety profile. Expanded cohorts are planned to better characterise: response rates within individual tumour types, define survival outcomes and common biomarkers.