Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis

Abstract

Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced Tcell activation and anti-tumor immunity. In this phase 1b study, registered at Clinical. gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2weeks and i.p. ipilimumab every 6weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n= 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3mg/kg i.p. nivolumab every 2weeks plus 1mg/kg ipilimumab every 6weeks. This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).