Abstract CT262: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: sarcomatoid carcinoma of lung (cohort 11)
Authors: Chae Young Kwang , Othus Megan , Patel Sandip , Sandhu Peeran , Corum Larry R. , Cetnar Jeremy P. , Rayani Shayan , Moseley Anna , Chung Liam Il-Young , Kim Hye Sung , McLeod Christine M. , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle 
Published: April 2024

Abstract
Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be effective in several malignancies but their potential role in rare solid cancers is yet to be established. This study presents the first results of ipilimumab and nivolumab in the sarcomatoid carcinoma of lung cohort (#11) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.
Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease (SD) &gt;6 months, and toxicity are secondary endpoints.
Results: Fourteen evaluable patients (median age, 64 years) with sarcomatoid carcinoma lung tumors were analyzed. ORR was 28.6% (4/14) with 1 CR and 3 PRs. The patient with CR has a duration of response (DoR) and OS of 32.4+ months. Three patients with PR showed 100% regression with resolution of one of two non-measurable non-target lesions (DoR 36.8 months), 92% regression (DoR 6.6 months), and 52% regression (DoR 23.0+ months), respectively. Clinical benefit rate (CBR; no progression &gt; 6months) was 50.0% (7/14). The median PFS was 6.1 months, median OS was 10.9 months. The most common adverse events were fatigue and dyspnea (46.2%, n=6 each), and pruritus and hypothyroidism (30.8%, n=4 each). Grade 3-4 adverse events occurred in 30.8% of patients (n=4). There were no adverse events that led to discontinuation. There was one grade 5 adverse event due to respiratory failure.
Conclusion: Ipilimumab plus nivolumab in sarcomatoid carcinoma of lung resulted in an ORR of 28.6% and CBR (SD&gt;6 months/PR/CR) of 50.0%, with PFS of 36.9, 32.4+, 23.0+, 17.0, 13.3, 6.6, and 6.6 months. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies are warranted.
Citation Format: Young Kwang Chae, Megan Othus, Sandip Patel, Peeran Sandhu, Larry R. Corum, Jeremy P. Cetnar, Shayan Rayani, Anna Moseley, Liam Il-Young Chung, Hye Sung Kim, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: sarcomatoid carcinoma of lung (cohort 11) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT262.