Efficacy and CNS Toxicity of Nivolumab and Ipilimumab in Rare Cancer Brain Metastases - A Multicenter Basket Trial Analysis (NCI/SWOG S1609)

Sep 22, 2026

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Evaluates the efficacy and safety of dual immune checkpoint inhibitors nivolumab plus ipilimumab for patients with brain metastases (BM) arising from rare cancers. Patients with and without BM received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks across more than 1,000 sites. Progression-free survival and overall survival were estimated by Kaplan–Meier with hazard ratios from Cox models. Systemic objective response rate used RECIST 1.1, while adverse events used CTCAE v5.0, with intracranial response assessed in a BM subset.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

Purpose and Methods

Results

Conclusions

Introduction

Efficacy and CNS Toxicity of Nivolumab and Ipilimumab in Rare Cancer Brain Metastases: A Multicenter Basket Trial Analysis (NCI/SWOG S1609) Manmeet S. Ahluwalia1, Sophie Solomon2, Sandip P. Patel3, Zouina Sarfraz1, Megan Othus2, Young K. Chae4, and Razelle Kurzrock5,6 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Purpose: To evaluate the efficacy and safety of dual immune checkpoint inhibitors (ICI) in patients with brain metastases (BM) from rare cancers.
Patients and Methods: Patients with and without BM received nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks; NCI/SWOG S1609 DART trial, NCT02834013) across > 1,000 sites. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method; hazard ratios (HR) with 95% confidence intervals (CI) were derived from Cox models. Systemic objective response rate (ORR) was assessed by RECIST version 1.1, and adverse events were graded using Common Terminology Criteria for Adverse Events version 5.0. Intracranial outcomes were assessed in a subset of patients with BM to evaluate the best intracranial response.
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Results: Among 727 patients, the systemic ORR was 11.5% in those without BM (n ¼ 707) and 10% in those with BM (n ¼ 20; P ¼ 0.76) . PFS and OS were similar between groups (PFS: HR ¼ 1. 29; 95% CI, 0.81–2. 07; P ¼ 0. 28; OS: HR ¼ 1. 36; 95% CI, 0.81–2.27; P ¼ 0.24) . Intracranial response was evaluable in 12 patients with BM (60%) . No intracranial complete or partial responses were observed, and six patients (50%) achieved intracranial stable disease as their best intracranial response. Grade ≥3 central nervous system toxicities occurred in 3% of patients without BM and 5% of those with BM (P ¼ 0.43) .
Conclusions: Dual ICI therapy showed comparable efficacy and safety in patients with and without BM.
See related commentary by Ricci and Rizzo, p. 1921 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Brain metastases (BM) are a common site of distant spread in lung, breast, melanoma, and renal cancers (1), affecting more than 200,000 individuals annually in the United States and are reported in 10% to 30% of all patients with cancer (2) . Historically, BM have 1Miami Cancer Institute, Baptist Health South Florida, Miami, Florida. 2Fred Hutch Cancer Center, Seattle, Washington. 3UC San Diego Moores Cancer Center, La Jolla, California. 4Division of Medical Oncology, Department of Medicine, Northwestern University, Chicago, Illinois. 5Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. 6WIN Consortium for Precision Medicine, Paris, France. Corresponding Authors: Manmeet S. Ahluwalia, Miami Cancer Institute, Baptist Health South Florida, 8900 North Kendall Drive, Miami, FL 33176 and Hebert Wertheim College of Medicine, Florida International University, 11200 Southwest 8t

FAQs

What was the purpose of the NCI/SWOG S1609 basket trial analysis?

To evaluate efficacy and safety of dual immune checkpoint inhibitors in patients with brain metastases from rare cancers, comparing outcomes between patients with and without BM.

How were efficacy and safety outcomes measured?

Progression-free survival and overall survival were estimated with Kaplan–Meier and hazard ratios from Cox models. Systemic response used RECIST v1.1, adverse events were graded with CTCAE v5.0, and intracranial outcomes were assessed in a BM subset.

What were the main findings for patients with brain metastases?

Systemic objective response rates were similar between groups, and progression-free survival and overall survival did not differ meaningfully. Intracranial response showed no complete or partial responses, with stable disease being the best intracranial response for some patients, and grade ≥3 central nervous system toxicities were low in both groups.

Sep 22, 2026

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