A randomized phase 2 trial of the IO102-IO103 (IDO and PD-L1) cancer vaccine plus pembrolizumab as neoadjuvant/adjuvant treatment of patients with solid tumors.

TPS2701 Background: Immune checkpoint inhibitors have transformed the treatment of multiple tumor types, including melanoma and squamous cell carcinoma of the head and neck (SCCHN). However, some patients (pts) with locally advanced disease still recur after surgery and adjuvant therapies. In melanoma, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab was shown to improve event-free survival (EFS) compared to adjuvant pembrolizumab only (1). In SCCHN, two cycles of neoadjuvant pembrolizumab resulted in a two-fold increase in the frequency of pathological tumor response compared with one cycle (2). IO102-IO103 is an investigational therapeutic cancer vaccine that targets both tumor and immune-suppressive cells in the tumor microenvironment. IO102-IO103 treatment promotes inflammation and potentiates anti-tumor activity via activation and expansion of T cells against IDO1 and/or PD-L1 positive cells. Treatment with IO102-IO103 plus nivolumab in anti-PD-1 naïve metastatic melanoma showed 80% objective response rate including 50% complete response and was well tolerated in a phase 1/2 trial (3). We aim to investigate the activity of IO102-IO103 plus pembrolizumab in the perioperative setting in melanoma and SCCHN. Methods: IOB-032//PN-E40 (NCT05280314) is a Phase 2, open-label, multi-cohort trial aiming to evaluate safety, anti-tumor and immunological activity of IO102-IO103 in combination with pembrolizumab as neoadjuvant and adjuvant treatment. Pts with resectable tumors classified as melanoma (Cohorts A and C) or SCCHN (Cohort B) are eligible. Cohorts A and B are single-arm 15 patient cohorts. Following completion of Cohort A, additional 30 stage III melanoma pts will be randomized 1:1 to receive neo-adjuvant treatment with either IO102-IO103 plus pembrolizumab or pembrolizumab alone (Cohort C). During the neoadjuvant period, study treatment is every 3 weeks (Q3W) for 3 cycles (melanoma) or 2-3 cycles (SCCHN). Surgery will be performed between 1 and 3 weeks after the last neoadjuvant dose, followed by adjuvant treatment with IO102-IO103 and pembrolizumab or pembrolizumab alone Q3W for 15 cycles. Pts in Cohort C with poor pathological response to pembrolizumab alone in the neoadjuvant phase (>10% residual viable tumor) may cross over to receive the combination treatment post-surgery at the discretion of the investigator. The primary endpoint is major pathological response (≤10% residual viable tumor) at surgery (central assessment). Secondary endpoints include safety, EFS and disease-free survival. Furthermore, paired pre- and post-treatment tumor tissue and blood samples will be collected for translational research. The study will be conducted in the US, EU and Australia and began enrolment in December 2023. 1. Patel, NEJM 2023. 2. Oliveira, Sci Immunol. 2023. 3. Kjeldsen, Nat Med. 2021. Clinical trial information: EudraCTNo.2022-502787-20-00; ClinicalTrials.govNo.NCT05280314 .