Logo image
Back
A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery
Journal article   Open access   Peer reviewed

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery

Evan Rosenbaum, Rashmi Chugh, Christopher W. Ryan, Mark Agulnik, Mohammed M. Milhem, Suzanne George, Robin L. Jones, Bartosz Chmielowski, Brian A. Van Tine, Hussein Tawbi, …
European journal of cancer (1990), Vol.176, pp.155-163
11/2022
DOI: 10.1016/j.ejca.2022.09.003
PMCID: PMC10204709
PMID: 36215947
url
https://doi.org/10.1016/j.ejca.2022.09.003View
Published (Version of record) Open Access

Abstract

Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. We conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response. A total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms. Clinicaltrials.gov identifier: NCT01141491 •Sarcomas overexpress gangliosides, which are attractive therapeutic targets.•In this trial, a trivalent ganglioside vaccine failed to prolong relapse-free survival.•The vaccine was generally safe, well tolerated and generated a serologic response.•New strategies are needed to elicit a clinically meaningful anti-ganglioside immune response.
 Adjuvant Ganglioside Sarcoma Vaccine

Details

Metrics

22 Record Views
13 Times Cited - Web of Science
Logo image