Abstract IO102-IO103 is an investigational immune-modulatory therapeutic cancer vaccine targeting tumor and immune-suppressive cells in the tumor microenvironment (TME) via activation and expansion of T cells against IDO1 and PD-L1-positive cells. Perioperative administration of pembrolizumab (pembro) has demonstrated significant improvement in event-free survival (EFS) for patients (pts) with resectable head and neck squamous cell carcinoma (HNSCC). Here we test IO102-IO103 plus pembro in the perioperative setting. IOB-032/PN-E40 (NCT05280314) is an open-label, multi-cohort, Phase 2 trial evaluating safety, anti-tumor and immunological activity of IO102-IO103 plus pembro as neoadjuvant/adjuvant treatment. Pts with resectable HNSCC (stage III−IV), regardless of human papillomavirus (HPV) status, received IO102-IO103 and pembro every 3 weeks (Q3W) for 2 or 3 cycles followed by surgery and risk-based standard of care radiotherapy (RT) ± chemotherapy (chemo). After recovery, adjuvant treatment with IO102-IO103 plus pembro was administered Q3W for up to 15 cycles. The primary endpoint is major pathological response (MPR; ≤10% residual viable tumor RVT) at surgery. Other key endpoints include: EFS, safety and vaccine-specific immune-responses. Between Dec 2023 and Nov 2024, 16 pts with resectable HNSCC (including 2 HPV- oropharyngeal carcinoma) were enrolled. All pts completed at least 2 cycles of neoadjuvant treatment. At data cutoff 18-Jul-2025, 13 (81. 3%) pts had undergone surgery and were evaluable for centrally determined pathological response. Median time to surgery was 34 days (range 29−134) from the first neoadjuvant dose. One pt refused surgery but wished to stay on treatment; 1 pt progressed and became inoperable, and 1 pt withdrew consent prior to surgery. Of 13 evaluable pts, 3 (23. 1%) had a pathological response with ≤50% RVT (pTR-2) by central review and 5 (38. 5%) had a pathological response per investigator review; both assessed 1 (7. 7%) pt as meeting the criteria for MPR (≤10%). At data cutoff, 11 (68. 8%) pts received adjuvant therapy after RT ± chemo, 4 of whom received chemoRT. Two pts decided not to initiate adjuvant treatment. In total, 3 (18. 8%) pts discontinued treatment due to adverse events; two of these were treatment-related (soft tissue edema, grade 3; injection-site lump, grade 1). EFS and analysis of treatment-associated changes in the TME will be presented, together with baseline characteristics including PD-L1 status. This is the first trial investigating an IDO1-PD-L1-immune-modulatory cancer vaccine plus anti-PD-1 therapy as perioperative treatment for HNSCC. The regimen was well-tolerated, and the implementation of neoadjuvant dosing and pathological assessment was feasible. Further follow-up will provide key insights into the potential benefit of adding IO102-IO103 to perioperative treatment with pembro. Citation Format: Barbara Burtness, Ravindra Uppaluri, Michael J. Dennis, Annette M. Lim, Richard A. Scolyer, Erin Alesi, Ayako Wakatsuki Pedersen, Amy Wesa, Ravi K. Adapala, Ulla Kring Hansen, Marcos Iglesias, Bushi Wang, Cecilie Abildgaard, Qasim Ahmad, Francois Ringeisen, Georgina V. Long, Robert I. Haddad. IOB-032/PN-E40: A phase 2 study of neoadjuvant/adjuvant IO102-IO103 cancer vaccine plus pembrolizumab in resectable HNSCC abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT240.
Burtness et al. (Fri,) studied this question.