Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results

被引：47

作者：

Glitza Oliva, Isabella C. ^{[1
]}

Ferguson, Sherise D. ^{[2
]}

Bassett Jr, Roland ^{[3
]}

Foster, Alexandra P. ^{[1
]}

John, Ida ^{[1
]}

Hennegan, Tarin D. ^{[1
]}

Rohlfs, Michelle ^{[1
]}

Richard, Jessie ^{[1
]}

Iqbal, Masood ^{[1
]}

Dett, Tina ^{[1
]}

Lacey, Carol ^{[1
]}

Jackson, Natalie ^{[1
]}

Rodgers, Theresa ^{[1
]}

Phillips, Suzanne ^{[1
]}

Duncan, Sheila ^{[4
]}

Haydu, Lauren ^{[4
]}

Lin, Ruitao ^{[1
,3
]}

Amaria, Rodabe N. ^{[1
]}

Wong, Michael K. ^{[1
]}

Diab, Adi ^{[1
]}

Yee, Cassian ^{[1
]}

Patel, Sapna P. ^{[1
]}

McQuade, Jennifer L. ^{[1
]}

Fischer, Grant M. ^{[1
]}

McCutcheon, Ian E. ^{[2
]}

O'Brien, Barbara J. ^{[5
]}

Tummala, Sudhakar ^{[5
]}

Debnam, Matthew ^{[6
]}

Guha-Thakurta, Nandita ^{[6
]}

Wargo, Jennifer A. ^{[4
]}

Burton, Elizabeth M. ^{[7
]}

Tawbi, Hussein A. ^{[1
]}

Davies, Michael A. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Neuroradiol, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX USA

来源：

NATURE MEDICINE | 2023年 / 29卷 / 04期

基金：

美国国家卫生研究院;

关键词：

METASTATIC MELANOMA; BRAIN METASTASES; CLINICAL-TRIALS; OPEN-LABEL; IPILIMUMAB;

D O I：

10.1038/s41591-022-02170-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256.

引用

页码：898 / 905

页数：18

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