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

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.