An investigational immunotherapy triplet combination is showing promise for the treatment of advanced solid tumors. Recruitment for the phase 2 study continues.
Jonathan W. Riess, MD, MS
IO102 and IO103 in combination with pembrolizumab (Keytruda) has elicited responses in patients with previously untreated, unresectable, or metastatic solid tumors, in a phase 2 study.1
Initial data from the trial came from 10 patients with non–small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (SCCHN), and urothelial bladder cancer (uBC). Of the 10 patients, 9 were evaluable for efficacy, and partial responses occurred in 4 patients. The combination also induced stable disease in 4 patients, and there was 1 patient with progressive disease. The safety of IO102, IO103, and pembrolizumab in this analysis was consistent with prior studies.
Trial Name: A Phase II Multi-Arm (Basket) Trial Investigating the Safety and Efficacy of IO102-IO103 in Combination With Pembrolizumab, as First-Line Treatment for Patients With Metastatic NSCLC, SCCHN, or Metastatic mUBC
ClinicalTrials.gov Identifier: NCT05077709
Sponsor: IO Biotech
Recruitment Contact: Eva Ehrnrooth, +45 3059 6091, ee@iobiotech.com or Anita Vedel Christiansen, +45 3110 9791, av@iobiotech.com
Completion Date: November 30, 2024
“Though tremendous advances in NSCLC have been made especially with the introduction of PD-L1 immune checkpoint inhibitors, many patients have tumors that are refractory to treatment, even lung cancers that have high expression of PD-L1. IO102 and IO103 stimulate activation of human T-cells against IDO and PD-L1 expressing cells, respectively, principal investigator Jonathan W. Riess, MD, MS, director of Thoracic Oncology, and associate professor of Medicine at UC Davis Health told Targeted Oncology™. “To address this unmet need we have initiated a study of IO-102 and IO-103 plus pembrolizumab in stage IV lung adenocarcinoma with high PD-L1 expression.
IO102 and IO103 in an investigational immunotherapy doublet which is designed to target immunosuppressive proteins like IDP and PD-L1.
“IO102 and IO103 stimulate activation of human T-cells against IDO and PD-L1 expressing cells, respectively, and they have been demonstrated to activate proinflammatory immune responses and cytotoxic killing of immunosuppressive cells in vitro. Thus, treatment with IDO and PD-L1 peptides in patients with cancer may activate the immune system to eradicate IDO- and PDL1 expressing tumor and immune cells in the tumor microenvironment, facilitating the activation and proliferation of effector T-cells against tumor cells, explained Riess. “In advanced melanoma, IO102-IO103 plus PD-1 inhibitor led to an 80% response rate and 43% complete response rate in a phase 1/2 clinical trial with vaccine-specific responses detected in the blood of >93% of patients during administration of these immunomodulatory peptides.”
The non-comparative, open-label, unblinded, basket trial of IO102 and IO103 used in combination with pembrolizumab will investigate the efficacy and safety of the triplet in approximately 90 patients with metastatic NSCLC, SCCHN, or uBC. The primary end point of the study is objective response rate (ORR) or progression-free survival (PFS) within a 6-month time frame. ORR will be accessed according to RECIST v1.1, and the PFS rate will be investigator assessed. The secondary end points of the study include PFS, duration of response, complete response rate, disease control rate, overall survival, time to response, and safety. As exploratory end points, biomarker will be evaluated to understand the correlation between biomarkers and clinical and immunologic response.2
To be included, patients must have histologically or cytologically confirmed disease and PD-L1 expression or a PD-L1 combined positive score. The level of PD-L1 expression must be ≥ 50% for the NSCLC cohort, ≥ 20 for the SCCHN cohort, and ≥ 10 for the uBC cohort. In addition, all patients must be 18 years of age or older with measurable disease, an ECOG performance score of 0 or 1, and adequate organ function.
The study excludes patients who were previously treated. It also excluded patients who have a life expectancy of less than 3 months, hypersensitivity to any of the agent used in the study, comorbidities, or active infections that may interfere with the effectiveness of any study drug.
Patients who meet the requirement to enroll are being recruited at 19 study sites across the United States, Spain, and the United Kingdom.
According to Riess, the investigators of the study look forward to presenting the results at an upcoming meeting.
REFERENCES:
1. IO Biotech provides business update. News release. IO Biotech. January 9, 2023. Accessed January 27, 2023. https://bit.ly/3WFFNQl
2. Reiss JW, Shaw P, Srinivasan D, et al. 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). J Clin Oncol. 2022; 40 (suppl 16). doi:10.1200/JCO.2022.40.16_suppl.TPS2699
