eligibility_summary
Advanced/metastatic solid tumor with KRAS mutation (no prior KRAS inhibitor), ECOG 0-1, >=1 measurable nonirradiated lesion. PDAC must be adenocarcinoma, NSCLC with drivers must have failed targeted therapy. Part 1: 2-3L PDAC/NSCLC/CRC, others refractory/intolerant. Part 2: 1L PDAC/CRC/NSCLC (NSCLC TPS>=50% or any TPS), no prior systemic tx. Exclude: pneumonitis/ILD, significant GI disease/bleeding, surgery/radiation, unstable effusions, PPI use, allergy, abnormal heme/renal/hepatic labs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1, open-label trial of PF-07985045, an oral small-molecule KRAS inhibitor, in KRAS-mutant advanced solid tumors (PDAC, CRC, NSCLC), as monotherapy and in combinations. Combinations/mechanisms: gemcitabine (antimetabolite) + nab-paclitaxel (taxane), cetuximab (EGFR monoclonal antibody), FOLFOX (5-FU antimetabolite + oxaliplatin platinum + leucovorin) ± bevacizumab (anti-VEGF mAb), pembrolizumab or sasanlimab (PD-1 checkpoint inhibitors) ± platinum/taxane/pemetrexed chemo, PF-07284892 (ARRY-558), a small-molecule SHP2 inhibitor. Targets/pathways: mutant KRAS and RAS-MAPK signaling (KRAS, SHP2), EGFR on tumor cells, VEGF-driven angiogenesis (endothelial cells), PD-1 on T cells (restoring antitumor immunity), and cytotoxic effects on rapidly dividing tumor cells (DNA synthesis/crosslinking, microtubules).