A phase II study presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting revealed promising results for the IO102-IO103 vaccine in combination with pembrolizumab as a first-line treatment for patients with non-small cell lung cancer (NSCLC). The trial, led by Riess et al., demonstrated encouraging overall response rates and a 6-month progression-free survival rate, coupled with a manageable safety profile.
Study Design and Patient Population
The open-label, multicenter, noncomparative trial enrolled 37 patients with metastatic, anti-PD-1 naive NSCLC who had a PD-L1 tumor proportion score of 50% or greater and no known targetable mutations. The median age of the patients was 71 years, with 51% being female. A significant portion of the participants were either current (24%) or former (65%) smokers.
Patients received subcutaneous injections of IO102-IO103, a first-in-class, dual-antigen, immune-modulatory vaccine, in 3-week cycles alongside pembrolizumab for up to two years. IO102-IO103 is designed to stimulate T-cell activation against indoleamine 2,3-dioxygenase 1 (IDO1) and PD-L1–positive cells within the tumor microenvironment.
The primary endpoint of the study was the overall response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included progression-free survival (PFS) and safety.
Efficacy and Safety Outcomes
Among the 31 patients evaluable for efficacy, the confirmed ORR was 48.4% (95% CI = 30%–67%), with 1 complete response and 14 partial responses. An additional 10 patients (32.3%) experienced stable disease, resulting in a disease control rate of 80.6%. The progression-free survival rate at 6 months was 61%.
Treatment-related adverse events of any grade were reported in 78.4% of patients (n = 29), with grade 3 or higher events occurring in 24.3% (n = 9). Serious adverse events were reported in 8.1% of patients (n = 3). The most common adverse event was injection-site reaction (32.4%; n = 12), all of which were grade 1 or 2.
Clinical Implications
"IO102-IO103/pembrolizumab as first-line treatment of PD-L1–high NSCLC showed promising ORR and 6-month PFS rate, with an acceptable safety profile," the study authors concluded. They noted that these data build upon previous encouraging clinical evidence of IO102-IO103 in combination with anti–PD-1 inhibitors across various cancers, including melanoma, NSCLC, and squamous cell carcinoma of the head and neck. Further follow-up is planned to assess PFS, duration of response, and exploratory biomarkers.
