Published Date: October 26, 2023

Full Text Article

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

Authors: Sandip P Patel, Megan Othus, Young Kwang Chae, Michael J Dennis, Sarah Gordon, David Mutch, Wolfram Samlowski, William R Robinson, Elad Sharon, Christopher Ryan, Gabby Lopez, Melissa Plets, Charles Blanke, Razelle Kurzrock

Clin Cancer Res. 2023 Oct 26. doi: 10.1158/1078-0432.CCR-23-2293. Online ahead of print.


PURPOSE: 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).

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

PMID: 37882676DOI: 10.1158/1078-0432.CCR-23-2293