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

Jennifer L. McQuade, Jade Homsi, Carlos A. Torres-Cabala, Roland Bassett, Rashmi Murthy Popuri, Marihella L. James, Luis M. Vence, Wen Jen Hwu

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number1274
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - Dec 19 2018

Fingerprint

Immunologic Adjuvants
Interleukin-2
Melanoma
Neoplasms
Proteins
Therapeutics
Safety
Maintenance
Immunologic Monitoring
Regulatory T-Lymphocytes

Keywords

  • HDIL-2
  • Immunotherapy
  • MAGE-A3 CI
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

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. / McQuade, Jennifer L.; Homsi, Jade; Torres-Cabala, Carlos A.; Bassett, Roland; Popuri, Rashmi Murthy; James, Marihella L.; Vence, Luis M.; Hwu, Wen Jen.

In: BMC Cancer, Vol. 18, No. 1, 1274, 19.12.2018.

Research output: Contribution to journalArticle

McQuade, Jennifer L. ; Homsi, Jade ; Torres-Cabala, Carlos A. ; Bassett, Roland ; Popuri, Rashmi Murthy ; James, Marihella L. ; Vence, Luis M. ; Hwu, Wen Jen. / 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. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
@article{76338abc75f548c3957541851c9270f8,
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",
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.",
keywords = "HDIL-2, Immunotherapy, MAGE-A3 CI, Melanoma",
author = "McQuade, {Jennifer L.} and Jade Homsi and Torres-Cabala, {Carlos A.} and Roland Bassett and Popuri, {Rashmi Murthy} and James, {Marihella L.} and Vence, {Luis M.} and Hwu, {Wen Jen}",
year = "2018",
month = "12",
day = "19",
doi = "10.1186/s12885-018-5193-9",
language = "English (US)",
volume = "18",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - 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

AU - McQuade, Jennifer L.

AU - Homsi, Jade

AU - Torres-Cabala, Carlos A.

AU - Bassett, Roland

AU - Popuri, Rashmi Murthy

AU - James, Marihella L.

AU - Vence, Luis M.

AU - Hwu, Wen Jen

PY - 2018/12/19

Y1 - 2018/12/19

N2 - 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.

AB - 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.

KW - HDIL-2

KW - Immunotherapy

KW - MAGE-A3 CI

KW - Melanoma

UR - http://www.scopus.com/inward/record.url?scp=85058892597&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058892597&partnerID=8YFLogxK

U2 - 10.1186/s12885-018-5193-9

DO - 10.1186/s12885-018-5193-9

M3 - Article

VL - 18

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 1274

ER -