TY - JOUR
T1 - 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
AU - Patel, Sandip P.
AU - Othus, Megan
AU - Chae, Young Kwang
AU - Dennis, Michael J.
AU - Gordon, Sarah
AU - Mutch, David
AU - Samlowski, Wolfram
AU - Rusty Robinson, William R.
AU - Sharon, Elad
AU - Ryan, Christopher
AU - Lopez, Gabby
AU - Plets, Melissa
AU - Blanke, Charles
AU - Kurzrock, Razelle
N1 - Publisher Copyright:
©2023 American Association for Cancer Research.
PY - 2024/1/10
Y1 - 2024/1/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85181761039&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-2293
DO - 10.1158/1078-0432.CCR-23-2293
M3 - Article
C2 - 37882676
AN - SCOPUS:85181761039
SN - 1078-0432
VL - 30
SP - 33
EP - 38
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -