eligibility_summary
Adults 18–75 with ECOG 0–1, ≥12‑week life expectancy, unresectable/metastatic solid tumors with centrally confirmed KRAS G12D, tumor tissue available, measurable disease per RECIST 1.1 (except dose escalation), and adequate labs. Exclude active/untreated CNS or meningeal mets, recent therapy/RT, unresolved ≥G2 toxicity, interstitial pneumonia, significant effusions/ascites, severe CV disease, active HBV/HCV, immunodeficiency/HIV/transplant, uncontrolled psych/substance issues, other investigator‑assessed risks.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT06385678 tests HRS-4642–based combos in advanced solid tumors with KRAS G12D. Interventions and mechanisms: - HRS-4642: selective small-molecule KRAS G12D inhibitor, blocks mutant KRAS signaling to suppress RAS/RAF/MEK/ERK (MAPK) pathway in KRAS G12D–driven tumor cells. - Adebrelimab: anti–PD-L1 monoclonal antibody (immune checkpoint inhibitor), restores T‑cell–mediated antitumor immunity by blocking PD-1/PD-L1. - Cetuximab: anti‑EGFR monoclonal antibody, inhibits EGFR signaling and may mitigate RTK feedback upon KRAS inhibition. - Pemetrexed: antifolate antimetabolite, inhibits thymidylate synthase, DHFR, and GARFT to block DNA synthesis. - Cisplatin/Carboplatin: platinum DNA crosslinkers, induce DNA damage/apoptosis. - SHR-9839: investigational drug, mechanism not specified in the registry. Targeted cells/pathways: KRAS G12D–mutant tumor cells, MAPK/ERK, EGFR, PD-1/PD-L1 immune axis, folate-dependent DNA synthesis, DNA damage pathways.