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.

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.

• Authors: Jennifer L McQuade, Jade Homsi, Carlos A Torres-Cabala, Roland Bassett, Rashmi Murthy Popuri, Marihella L James, Luis M Vence, Wen-Jen Hwu
• Journal: BMC cancer (BMC Cancer) Vol. 18 Issue 1 Pg. 1274 (Dec 19 2018) ISSN: 1471-2407 [Electronic] England
• PMID: 30567529 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Interleukin-2
• MAGEA3 protein, human
• Neoplasm Proteins
• Recombinant Proteins

Topics

• Adjuvants, Immunologic
• Adult
• Antigens, Neoplasm (administration & dosage, genetics, immunology)
• Female
• Humans
• Immunotherapy
• Interleukin-2 (administration & dosage, genetics, immunology)
• Male
• Melanoma (drug therapy, genetics, immunology, pathology)
• Middle Aged
• Neoplasm Proteins (administration & dosage, genetics, immunology)
• Neoplasm Staging
• Recombinant Proteins (administration & dosage, genetics, immunology)
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Treatment Outcome