Phase 2 study of the IDO/PD-L1-targeted immune-modulatory vaccine, IO102-IO103, plus pembrolizumab as first-line treatment for metastatic non–small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), or urothelial bladder cancer (UBC).
Authors: Riess Jonathan W. , Shaw Paul , Srinivasan Devraj , Garrido Pilar , Vuky Jacqueline , Chaney Marya F. , O'Neill Shane , Alavi Alireza , McDowell Diane Opatt , Ehrnrooth Eva , Cohen Ezra 
Published: June 2022

TPS2699 Background: Immunotherapy has transformed the treatment of NSCLC and other solid tumors, such as SCCHN and UBC. However, even with standard-of-care anti-PD-1/PD-L1 therapies, few patients achieve durable benefit even when PD-L1 is overexpressed. IO102-IO103 is a potentially first-in-class, dual-antigen, immune-modulatory therapy that stimulates T cells to target tumoral immune escape via key checkpoint molecules IDO and PD-L1. It is thought that activating IDO/PD-L1-specific T cells in cancer patients through vaccination may support anticancer immunity by restricting immunosuppressive signaling and restoring the tumor immune microenvironment to render the tumor more susceptible to anti-PD-1 blockade. Thus there is a rationale for combining IO102-IO103 with anti-PD-1 therapy in the first-line treatment of metastatic tumors, such as NSCLC, SCCHN, or UBC. Combined IO102-IO103 and anti-PD-1 therapy (nivolumab) has already shown a robust signal of clinical activity (overall response rate [ORR], 80%; complete response rate [CRR], 43%; median progression-free survival [PFS], 26 months) and was well tolerated with minimal added toxicity to nivolumab in a Phase 1/2 study of anti-PD1-naïve patients with metastatic melanoma (Kjeldsen, et al. Nat Med 2021). Methods: This is a Phase 2, international, multicenter (US and Europe), non-comparative, open-label, multi-arm (basket) trial (EudraCT No. 2021-003026-69; ClinicalTrials.gov No. NCT05077709). Patients with recurrent, unresectable or metastatic solid tumors in 3 indications and no prior treatments for metastatic disease are being enrolled: NSCLC with a PD-L1 Tumor Proportion Score (TPS) ≥50% (Arm A); SCCHN with PD-L1 Combined Positive Scores (CPS) ≥20 (Arm B); or UBC with PD-L1 CPS ≥10 and not eligible for platinum-containing chemotherapy (Arm C). All patients, ̃30 in each arm, will receive 3-week cycles of IO102-IO103 (85-85 µg on Day [D] 1 and 8 of Cycle 1 and 2, and D1 thereafter) subcutaneously plus pembrolizumab (200 mg on D1) intravenously, for up to 2 years. Primary endpoints are ORR by RECIST v1.1 or 6-month PFS rate by investigator assessment (to be analyzed either 6 months after last patient started treatment or after target ORR is achieved, whichever is earliest). Secondary endpoints include PFS, duration of response, complete response rate, disease control rate, time to response, overall survival, and safety. Exploratory endpoints include biomarker and immune marker correlative studies, and PFS by iRECIST. The trial will assess the opportunity for a positive risk–benefit based on 2 efficacy boundaries for the ORR and 6-month PFS rate in each arm, with cohort expansion permitted if a clinically relevant efficacy signal is observed. Clinical trial information: EudraCT No. 2021-003026-69; ClinicalTrials.gov No. NCT05077709.