ICTriplex (chemotherapy + immune checkpoint inhibition + targeted therapy) in advanced/refractory malignancies: A personalized treatment program.

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Background: Advanced and refractory malignancies remain associated with poor outcomes and limited treatment options. While chemotherapy (CT), immune checkpoint inhibitors (ICIs), and targeted therapy (TT) each demonstrate benefit in selected settings, resistance commonly develops. ICTriplex is a personalized regimen combining CT, ICIs, and TT to leverage complementary mechanisms and non-overlapping toxicities. Our preliminary experience has been previously reported at ASCO meetings (2019–2024) and in JCO. We present updated efficacy and survival outcomes with extended follow-up. Methods: Between March 2017 and February 2026, 73 evaluable patients with advanced malignancies were treated. Median age was 58 years; 40 female and 33 male. Tumor types: lung (14), colorectal (12), pancreatic (11), biliary tract (6), breast (6), ovarian (4), sarcoma (4), glioblastoma (3), melanoma (3), gastric (3), cervical (2), and others (5). Most patients had received prior CT, ICIs, and/or TT. Treatment was individualized based on diagnosis, prior therapy, and genomic profiling. Most commonly used agents are: ICI; nivolumab, atezolizumab, ipilimumab, and pembrolizumab; CT; taxanes, gemcitabine, and platinum agents; TT; bevacizumab and erlotinib. Radiographic response was assessed by RECIST v1.1 and metabolic response by PET/CT. Complete remission (CR) required complete metabolic resolution. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methodology. Results: Objective responses were observed across multiple tumor types. CR occurred in lung, pancreatic, and biliary tract cancers. Lung cancer patients with brain metastases achieved complete metabolic resolution without radiation. Median PFS was 9 months, and median OS was 16.4 months. CR rate was 47.9%, PR was 39.7%, and overall remission 87.6%. CR was significantly associated with improved outcomes: median PFS 15.4 vs 5.8 months and median OS 41.2 vs 10.9 months (both p<0.001). On Cox regression, CR reduced the risk of progression (HR 0.36) and death (HR 0.25). Prior treatment exposure did not significantly affect outcomes. Toxicity was manageable; three patients experienced fatal complications possibly related to ICIs. Conclusions: ICTriplex achieved significantly high remission rates and encouraging survival in a heterogeneous, heavily pretreated population. These findings confirm and extend our previously reported data and support ICTriplex as an appropriate option for patients with advanced malignancies who exhausted conventional therapy.