腹膜癌病
医学
无容量
卵巢癌
肿瘤科
内科学
妇科癌症
癌症
免疫疗法
结直肠癌
作者
Anne Knisely,Erin Hinchcliff,Bryan Fellman,Ann Mosley,Kathryn Lito,Sara E. Hull,Shannon N. Westin,Anil K. Sood,Kathleen M. Schmeler,Jolyn Taylor,Steven Y. Huang,Rahul A. Sheth,Karen H. Lu,Amir A. Jazaeri
出处
期刊:Med
[Elsevier]
日期:2024-04-01
卷期号:5 (4): 311-320.e3
标识
DOI:10.1016/j.medj.2024.02.003
摘要
Background Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. Methods In this phase 1b study, registered at Clinical.Trials.gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, 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). Findings 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 14.8 months (range: 4.1–20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. Conclusions i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. Funding 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).
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