| Title: |
A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma |
| Authors: |
Jennifer L. McQuade, Jade Homsi, Carlos A. Torres-Cabala, Roland Bassett, Rashmi Murthy Popuri, Marihella L. James, Luis M. Vence, Wen-Jen Hwu |
| Source: |
BMC Cancer, Vol 18, Iss 1, Pp 1-9 (2018) |
| Publisher Information: |
BMC, 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Melanoma, Immunotherapy, HDIL-2, MAGE-A3 CI, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Background HDIL-2 is approved for advanced melanoma based on its durable antitumor activity. MAGE-A3 cancer immunotherapeutic (MAGE-A3 CI) is a recombinant MAGE-A3 protein combined with an immunostimulant adjuvant system and has shown antitumor activity in melanoma. We assessed the safety and anti-tumor activity of HDIL-2 combined with MAGE-A3 CI in advanced melanoma. Methods Patients with unresectable Stage III or Stage IV MAGE-A3-positive melanoma were enrolled in this phase II study. Treatment included an induction phase of MAGE-A3 CI plus HDIL-2 for 8 cycles followed by a maintenance phase of MAGE-A3 CI monotherapy. The primary endpoints were safety and objective response assessed per RECIST v1.1. Immune biomarker and correlative studies on tumor and peripheral blood were performed. Results Eighteen patients were enrolled. Seventeen patients were evaluable for safety and sixteen for response. Responses occurred in 4/16 (25%) patients with 3 complete responses, and stable disease in 6/16 (38%) patients with a disease control rate of 63%. The median duration of response was not reached at median follow-up of 36.8 months. Induction therapy of HDIL-2 + MAGE-A3 CI had similar toxicities to those reported with HDIL-2 alone. Maintenance MAGE-A3 monotherapy was well-tolerated. Increased immune checkpoint receptor expression by circulating T regulatory cells was associated with poor clinical outcomes; and responders tended to have increased tumor infiltrating T cells in the baseline tumor samples. Conclusions The safety profile of HDIL-2 + MAGE-A3 CI was similar to HDIL-2 monotherapy. Maintenance MAGE-A3 CI provides robust anti-tumor activity in patients who achieved disease control with induction therapy. Immune monitoring data suggest that MAGE-A3 CI plus checkpoint inhibitors could be a promising treatment for MAGE-A3-positive melanoma. Trial registration ClinicalTrials.gov, NCT01266603. Registered 12/24/2010, https://clinicaltrials.gov/ct2/show/NCT01266603 |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1471-2407 |
| Relation: |
http://link.springer.com/article/10.1186/s12885-018-5193-9; https://doaj.org/toc/1471-2407 |
| DOI: |
10.1186/s12885-018-5193-9 |
| Access URL: |
https://doaj.org/article/a2e99d3cbedd4f4e820bcd11f4488ad1 |
| Accession Number: |
edsdoj.2e99d3cbedd4f4e820bcd11f4488ad1 |
| Database: |
Directory of Open Access Journals |
|
Full text is not displayed to guests. |
Login for full access.
|
