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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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, i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks. The primary endpoint was overall response rate [ORR; complete response (CR) þ partial response (PR)] by quantitative serum beta human chorionic gonadotropin (b-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, 3 of 4 patients responded [ORR ¼ 75% (CR, 25%, n ¼ 1, tumor mutation burden ¼ 1 mutation/megabase; PD-L1 tumor proportion score ¼ 50%); PR, 50%, n ¼ 2)]. Responders included malignant gestational trophoblastic neoplasm (n ¼ 1, CR, PFS 11þ months) and choriocarcinoma (n ¼ 2, both PRs, PFS 10þ and 6þ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% [95% confidence interval (CI), 43%–100%], and the median PFS was not reached (range, 35–339þ 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 of 4 patients achieved ongoing objective responses with a reasonable safety profile at 6–11þ months.

Original languageEnglish
Pages (from-to)33-38
Number of pages6
JournalClinical Cancer Research
Volume30
Issue number1
DOIs
StatePublished - Jan 10 2024

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