756 A phase 2 trial of the IO102-IO103 cancer vaccine plus pembrolizumab: results from the first-line (1L) cohort of PD-L1 high metastatic non-small cell lung cancer (NSCLC)

<h3>Background</h3> Anti-programmed cell death-1 (PD1) monotherapy is used in 1L NSCLC with PD-L1 high (≥50%) and without actionable genomic alterations; KEYNOTE-042 showed an objective response rate (ORR) to single-agent pembrolizumab in this population of 39%. IO102-IO103 is an off-the-shelf therapeutic cancer vaccine that enhances anti-tumor activity by activating and expanding T cell response against indoleamine 2,3-dioxygenase 1 (IDO1) and PD-L1 positive cells, targeting both tumor and immune-suppressive cells in the tumor microenvironment. Results from a phase 1/2 trial of anti-PD1 naïve metastatic melanoma patients treated with IO102-IO103/nivolumab demonstrated deep and durable responses with 25.5 months as median progression-free survival (PFS); treatment was well tolerated. Enrollment is complete in the phase 3 trial of IO102-IO103/pembrolizumab in patients with advanced 1L melanoma. <h3>Methods</h3> This phase 2, non-comparative, open-label, multi-center, multi-cohort trial enrolled metastatic anti-PD1 naïve NSCLC patients with PD-L1 tumor proportion score ≥50%, without known targetable mutations. Three-week cycles of subcutaneous IO102-IO103 (85–85 μg on day 1 and 8 of Cycle 1 and 2, then day 1 only) in combination with pembrolizumab (200 mg on day 1) were administered to patients for ≤2 years. Primary endpoint was ORR by RECIST 1.1 (the efficacy evaluable population included patients who received ≥2 cycles of treatment). Secondary endpoints included PFS and safety. <h3>Results</h3> At data cut-off (May 27, 2024), 37 patients were enrolled: median age 71 years, 51% female, 24% and 65% current and former smokers, respectively. Of 31 patients considered evaluable for efficacy, 1 had complete response and 14 had partial response (PR) (confirmed ORR 48.4%; 95% CI 30–67); 10 patients (32.3%) had stable disease and 6 (19.4%) had progressive disease. Disease control rate is 80.6%. PFS at 6 months was 61%. Treatment-related adverse events of any grade were reported in 29 patients (78.4%) with 9 (24.3%) grade ≥3 and 3 (8.1%) serious events. Injection-site reaction was the most common adverse event reported (n=12; 32.4%), all grade 1–2. <h3>Conclusions</h3> IO102-IO103/pembrolizumab as 1L treatment of PD-L1 high NSCLC showed promising ORR and 6-month PFS rate, with acceptable safety profile. These data build on the encouraging clinical evidence of IO102-IO103 in combination with anti-PD1 inhibitor, including earlier reported data in melanoma, NSCLC and squamous cell carcinoma of head and neck. At the time of data cut-off, a positive trend in median PFS was observed. Longer follow-up for PFS and duration of response, along with exploratory biomarkers are planned to be presented at the meeting. <h3>Acknowledgements</h3> Medical writing and editorial support for the development of this abstract, under the direction of the authors, were provided by Edward Potts and Beverly La Ferla of Ashfield MedComms, an Inizio company. <h3>Trial Registration</h3> EudraCT No. 2021-003026-69; ClinicalTrials.gov No. NCT05077709. <h3>Ethics Approval</h3> USA: WCG • IRB00000533 o 0101 – UC Davis o 0102 – Mid Florida o 0105 – City of Hope o 0108 – UC San Diego o 0111 – UPenn o 0112 – VCS 0103 – Univ of Toledo • The University of Toledo Human Research Protection Program Biomedical IRB • IRB number: 301251 • FWA00010686 0106 – Montefiore • Brany IRB • IRB#00000080 0107 – OHSU • OHSU IRB • IRB00000471 • FWA00000161 0113 – Johns Hopkins • Office of Human Subjects Research IRB • IRB00370966 • FWA00005752 (JH University School of Medicine) • FWA00006087 (JH Health System and JH Hospital) UK: • Name of EC: London - Westminster Research Ethics Committee • EC reference: 21/LO/0544.