Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Tumor Microenvironment Gene Engineering with LOAd703 in Patients with Solid Malignancies: LOKON002 Phase I/IIb Clinical Trial.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыНазвание и аннотация: Перевод пока не подготовлен
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Hahn Amanda, Irenaeus Sandra, Sandin Linda C, Nordström Clara, Wenthe Jessica, Lövgren Tanja, Eriksson Emma, Alsaqal Salem, Pahnke Simon, Sundin Anders, Leja Jarblad Justyna, Gustafsson Liljefors Maria, Loskog Angelica, Ullenhag Gustav J
Аннотация
PURPOSE: Patients with advanced cancer have a poor prognosis and need for novel treatments. LOAd703 is a tumor microenvironment (TME) gene engineering viral vector encoding genes targeting the CD40 and 4-1BB pathways. In this study, tolerability (primary endpoint), response activity, and the capacity to inflame the TME were evaluated.
PATIENTS AND METHODS: In an open-label, single-arm phase I/IIb clinical trial (NCT03225989), a maximum of eight intratumoral injections of LOAd703 were administered biweekly, combined with a gemcitabine-based chemotherapy regimen, either standard-of-care treatment or conditioning gemcitabine if no standard options were available. Dose escalation followed a standard 3 + 3 design (phase I) and, to optimize dosage, the two highest dose levels were expanded in phase II.
RESULTS: Forty-one patients were enrolled with pancreatic (n = 29), colorectal (n = 5), ovarian (n = 4), and biliary cancers (n = 3). Treatment was generally well tolerated. The most common LOAd703-related adverse events were pyrexia (76%), chills (39%), and fatigue (34%), mostly grade 1 to 2. The overall response rate (ORR) was 0 in the LOAd703 dose cohort 5 × 1010 viral particles (VP), 25% in 1 × 1011 VP, and 12% in 5 × 1011 VP. All patients with an objective response had pancreatic cancer and received first-line treatment (ORR, 35%). The TME showed a significant upregulation of Th1 immunity biomarkers at week 13 posttreatment initiation.
CONCLUSIONS: TME gene engineering using LOAd703 inflamed immune cold tumors and was followed by long-term stabilized disease in several patients. Further evaluation of LOAd703 together with chemotherapy and/or checkpoint inhibitors is warranted.
PATIENTS AND METHODS: In an open-label, single-arm phase I/IIb clinical trial (NCT03225989), a maximum of eight intratumoral injections of LOAd703 were administered biweekly, combined with a gemcitabine-based chemotherapy regimen, either standard-of-care treatment or conditioning gemcitabine if no standard options were available. Dose escalation followed a standard 3 + 3 design (phase I) and, to optimize dosage, the two highest dose levels were expanded in phase II.
RESULTS: Forty-one patients were enrolled with pancreatic (n = 29), colorectal (n = 5), ovarian (n = 4), and biliary cancers (n = 3). Treatment was generally well tolerated. The most common LOAd703-related adverse events were pyrexia (76%), chills (39%), and fatigue (34%), mostly grade 1 to 2. The overall response rate (ORR) was 0 in the LOAd703 dose cohort 5 × 1010 viral particles (VP), 25% in 1 × 1011 VP, and 12% in 5 × 1011 VP. All patients with an objective response had pancreatic cancer and received first-line treatment (ORR, 35%). The TME showed a significant upregulation of Th1 immunity biomarkers at week 13 posttreatment initiation.
CONCLUSIONS: TME gene engineering using LOAd703 inflamed immune cold tumors and was followed by long-term stabilized disease in several patients. Further evaluation of LOAd703 together with chemotherapy and/or checkpoint inhibitors is warranted.