A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

Abstract

PURPOSE:

Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).

PATIENTS AND METHODS:

We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.

RESULTS:

Thirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.

CONCLUSIONS:

Ipilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.

• Authors: Sandip P Patel, Megan Othus, Young Kwang Chae, Francis J Giles, Donna E Hansel, Preet Paul Singh, Annette Fontaine, Manisha H Shah, Anup Kasi, Tareq Al Baghdadi, Marc Matrana, Zoran Gatalica, W Michael Korn, Jourdain Hayward, Christine McLeod, Helen X Chen, Elad Sharon, Edward Mayerson, Christopher W Ryan, Melissa Plets, Charles D Blanke, Razelle Kurzrock
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 10 Pg. 2290-2296 (05 15 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31969335 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• CTLA-4 Antigen
• CTLA4 protein, human
• Ipilimumab
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Nivolumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• CTLA-4 Antigen (antagonists & inhibitors)
• Female
• Follow-Up Studies
• Humans
• Ipilimumab (administration & dosage)
• Male
• Middle Aged
• Neuroendocrine Tumors (drug therapy, pathology)
• Nivolumab (administration & dosage)
• Prognosis
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Prospective Studies
• Rare Diseases (drug therapy, pathology)
• Survival Rate