TY - JOUR
T1 - Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease
T2 - phase 1 trial interim results
AU - Glitza Oliva, Isabella C.
AU - Ferguson, Sherise D.
AU - Bassett, Roland
AU - Foster, Alexandra P.
AU - John, Ida
AU - Hennegan, Tarin D.
AU - Rohlfs, Michelle
AU - Richard, Jessie
AU - Iqbal, Masood
AU - Dett, Tina
AU - Lacey, Carol
AU - Jackson, Natalie
AU - Rodgers, Theresa
AU - Phillips, Suzanne
AU - Duncan, Sheila
AU - Haydu, Lauren
AU - Lin, Ruitao
AU - Amaria, Rodabe N.
AU - Wong, Michael K.
AU - Diab, Adi
AU - Yee, Cassian
AU - Patel, Sapna P.
AU - McQuade, Jennifer L.
AU - Fischer, Grant M.
AU - McCutcheon, Ian E.
AU - O’Brien, Barbara J.
AU - Tummala, Sudhakar
AU - Debnam, Matthew
AU - Guha-Thakurta, Nandita
AU - Wargo, Jennifer A.
AU - Burton, Elizabeth M.
AU - Tawbi, Hussein A.
AU - Davies, Michael A.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151335242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151335242&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-02170-x
DO - 10.1038/s41591-022-02170-x
M3 - Article
C2 - 36997799
AN - SCOPUS:85151335242
SN - 1078-8956
VL - 29
SP - 898
EP - 905
JO - Nature medicine
JF - Nature medicine
IS - 4
ER -