A phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in patients with gestational trophoblastic neoplasia

• Published in: Clinical cancer research 2024-01, Vol.30 (1), p.33-38
• Main Authors: Patel, Sandip P, Othus, Megan, Chae, Young Kwang, Dennis, Michael J, Gordon, Sarah, Mutch, David, Samlowski, Wolfram, Robinson, William R, Sharon, Elad, Ryan, Christopher, Lopez, Gabby, Plets, Melissa, Blanke, Charles, Kurzrock, Razelle
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-2293

The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). This prospective, open label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN. Eligible patients received nivolumab 240 mg intravenously (IV) every 2 weeks and ipilimumab 1 mg/kg IV every 6 weeks. The primary endpoint was overall response rate [ORR; complete response (CR) + partial response (PR)] by quantitative serum β-hCG; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Four patients with refractory GTN enrolled and received therapy. At 11 months of ongoing follow-up, three of four patients responded [ORR = 75% (CR, 25%, n=1, tumor mutation burden=1 mutation/megabase; PD-L1 tumor proportion score=50%); PR, 50%, n=2)]. Responders included malignant gestational trophoblastic neoplasm (n=1, CR, PFS 11+ months) and choriocarcinoma (n=2, both PRs, PFS 10+ and 6+ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% (95% confidence interval: 43-100%), and the median PFS was not reached (range, 35-339+ days); all 4 patients were alive at last follow-up. Two patients experienced grade 3 immune-related toxicity (arthralgia and colitis); there were no grade ≥ 4 events. Ipilimumab plus nivolumab demonstrated efficacy in chemotherapy-refractory GTN, an ultra-rare cancer affecting young women. Three out of four patients achieved ongoing objective responses with a reasonable safety profile at 6-11+ months.