Adding the CMB305 vaccine regimen to atezolizumab treatment does not improve survival outcomes in patients with soft-tissue sarcomas expressing NY-ESO-1, according to phase 2 results published in the Journal of Clinical Oncology.
Patients receiving CMB305 and atezolizumab did have significantly higher rates of antibody response and NY-ESO-1-specific T-cell response than patients who received atezolizumab alone.
“CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist,” the study authors explained.
They noted that the high frequency and homogeneity of NY-ESO-1 expression in synovial sarcoma (SS) and myxoid liposarcoma (MLS) make these tumors ideal for CMB305 vaccination.
With that in mind, the researchers conducted a phase 2 study (ClinicalTrials.gov Identifier: NCT02609984) to compare CMB305 plus atezolizumab with atezolizumab alone in patients with SS and MLS.
The study enrolled 89 patients at 18 sites in the United States. The patients’ mean age was 46.4 years (range, 21-83 years), and 55.1% had received 2 or more prior lines of chemotherapy.
The patients were randomly assigned to receive CMB305 with atezolizumab (n=45) or atezolizumab alone (n=44). A high level of NY-ESO-1 expression (>75%-100%) was observed in 80% of patients in the combination arm and 86% of those in the control arm.
Treatment-related adverse events (TRAEs) occurred in 75.6% of patients in the combination arm and 58.1% of those in the control arm. Four patients in each arm had grade 3 or higher TRAEs.
Grade 3 or higher TRAEs in the combination arm included thrombocytopenia, nausea, and influenza-like illness (n=1); respiratory failure and pneumonitis (n=1); hypertension (n=1); and lymphopenia (n=1).
Grade 3 or higher TRAEs in the control arm included increased ALT and AST (n=1), hypokalemia and influenza-like illness (n=1), elevated ALT (n=1), and pulmonary embolism (n=1).
The median progression-free survival was 2.6 months for the combination arm and 1.6 months for the control arm (hazard ratio, [HR], 0.9; 95% CI, 0.6-1.3; P =.49).
Both arms had a median overall survival of 18 months (HR, 1.2; 95% CI, 0.7-2.1; P =.47).
The rate of treatment-induced, NY-ESO-1-specific T-cell response was significantly higher in the combination arm than in the control arm — 53.8% and 15%, respectively (P =.01).
NY-ESO-1-specific antibody responses were also significantly higher in the combination arm than in the control arm — 50% and 0%, respectively (P <.0001).
In a post hoc analysis of all dosed patients, the median overall survival was longer in the subset of patients with anti-NY-ESO-1 T-cell immune responses while on therapy (HR, 0.3; P =.02).
“This study serves as a benchmark for SS and MLS,” the study authors wrote. “Prime-boost immunotherapies similar to CMB305 may be useful in different clinical contexts, such as providing a maintenance stimulus for NY-ESO-1-engineered T cells.”
Disclosures: This research was supported by Immune Design Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Chawla SP, Van Tine BA, Pollack SM, et al. Phase II randomized study of CMB305 and atezolizumab compared with atezolizumab alone in soft-tissue sarcomas expressing NY-ESO-1. J Clin Oncol. Published online July 14, 2021. doi:10.1200/JCO.20.03452