eligibility_summary
Inclusion: ≥18 with unresectable/metastatic gastric/GEJ/esophageal adeno or SCC, RECIST measurable/evaluable, biopsy feasible (PI may waive), known HER2 (escalation HER2−, expansion HER2±), no prior therapy for advanced disease (some prior neo/adjuvant/RT allowed), ECOG 0–1, adequate organs, CPK<Gr2, stable statin, LVEF≥LLN (Cohort B), contraception. Exclusion: alt cancer remedies, other trials, active CNS mets, allergy to study drugs, QTc>470/TdP-risk meds, ILD≥G2, live vaccine<30d, malabsorption, uncontrolled illness, pregnancy/breastfeeding, HIV CD4<350/recent OI or ART DDI, active autoimmune disease (exceptions), steroids>10 mg.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I study of CA-4948 plus mFOLFOX7 and a PD-1 inhibitor, with trastuzumab added for HER2+ disease. CA-4948 (emavusertib) is an oral small-molecule IRAK4 inhibitor that blocks MyD88/TLR/IL-1R signaling, reducing NF-kappaB activation and myeloid-driven immunosuppression to enhance antitumor responses. mFOLFOX7: 5-fluorouracil (antimetabolite inhibiting thymidylate synthase), leucovorin (enhances 5-FU), and oxaliplatin (platinum DNA crosslinker) to kill proliferating tumor cells. Nivolumab/pembrolizumab are IgG4 monoclonal antibodies blocking PD-1 on T cells, restoring cytotoxic activity. Trastuzumab is an IgG1 anti-HER2 antibody that inhibits HER2 signaling and mediates ADCC in HER2+ tumors. Targets/pathways: IRAK4-MyD88-NF-kappaB in tumor and myeloid cells, PD-1/PD-L1 checkpoint on T cells/tumor, HER2/ERBB2 on tumor cells, DNA synthesis (TS) and DNA integrity in cancer cells.