IO Biotech, a clinical-stage biopharmaceutical company, has announced the completion of enrollment in its Phase 2 basket trial (IOB-032/PN-E40) evaluating IO102-IO103, an off-the-shelf therapeutic cancer vaccine, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). The trial focuses on patients with resectable melanoma or squamous cell carcinoma of the head and neck (SCCHN) undergoing neoadjuvant and adjuvant treatment. The early completion of enrollment marks a significant step in exploring the potential of IO102-IO103 in earlier stages of disease progression across various solid tumors.
The multicenter, multi-cohort trial enrolled 93 patients across sites in the United States, Europe, and Australia. The study aims to assess the anti-tumor activity, safety, and biomarker data of the combination therapy. Initial data from the trial is anticipated in 2025.
Trial Design and Endpoints
The IOB-032/PN-E40 trial (NCT05280314) includes three cohorts: Cohorts A and B are single-arm cohorts consisting of 18 melanoma patients and 16 SCCHN patients, respectively, receiving IO102-IO103 with pembrolizumab. Cohort C involves 59 melanoma patients randomized 1:1 to either the combination of IO102-IO103 with pembrolizumab or pembrolizumab alone.
In the neoadjuvant period, treatment is administered every 3 weeks (Q3W) for 3 cycles (melanoma) or 2-3 cycles (SCCHN). Surgery is scheduled 4-9 weeks after the start of neoadjuvant treatment, followed by adjuvant treatment with the same regimen for 15 cycles. Patients in Cohort C with poor pathological response to pembrolizumab alone (>10% residual viable tumor) may cross over to combination treatment post-surgery.
The primary endpoint is major pathological response (MPR) at surgery, defined as ≤10% residual viable tumor (central assessment). Secondary endpoints include pathological complete response (pCR), overall response rate (ORR), disease-free survival (DFS), event-free survival (EFS), and safety.
IO102-IO103: An Immunomodulatory Approach
IO102-IO103 is an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine. It is designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells.
IO Biotech is also conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma. Data from this trial is also expected in the first half of 2025.
Expert Commentary
"We are pleased to have completed enrollment early in this study, as it signifies an important step in exploring the potential of our investigational therapeutic cancer vaccine, IO102-IO103, across a range of solid tumors at an earlier stage of disease progression," said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. "Our off-the-shelf cancer vaccine is designed to be a readily available option for patients and has demonstrated encouraging clinical activity without significant systemic toxicity across three first line advanced cancer indications – melanoma, lung cancer and head and neck cancer."
Qasim Ahmad, MD, Chief Medical Officer of IO Biotech, added, "The importance of systemic immunotherapy in the perioperative setting and its potential to change early treatment paradigms for a variety of cancers cannot be understated. This approach is being recognized as a critical opportunity to improve outcomes for patients by reducing the risk of recurrence and improving long-term survival."
