eligibility_summary
Eligible: advanced unresectable/metastatic KRAS‑mutant solid tumors, ECOG 0–1, ≥1 measurable non‑irradiated lesion. NSCLC: any KRAS except previously treated G12C, if other drivers, must have failed targeted therapy. Part1/2a: after standard care (PDAC, NSCLC incl platinum+IO, CRC 1–2 lines). Part2b: PDAC 1L, CRC 2–3L or 1L, NSCLC 1L (TPS ≥50% or any). Excludes pneumonitis/ILD, autoimmune on steroids, ≥G2 neuropathy, GI disease/bleeding, recent surgery/radiation, drug contraindications, heme/renal/hepatic dysfunction.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1, open-label trial of PF-07934040 (PF-4040), an oral small-molecule pan-KRAS inhibitor, in adults with advanced KRAS-mutant solid tumors (NSCLC, CRC, PDAC). Arms: monotherapy and combinations—PDAC 1L: PF-07934040 + gemcitabine (antimetabolite) + nab-paclitaxel (taxane), CRC 2-3L: + cetuximab (EGFR mAb), CRC 1L: + FOLFOX (5-FU antimetabolite, oxaliplatin platinum, leucovorin) + bevacizumab (VEGF-A mAb), NSCLC 1L: + pembrolizumab (PD-1 mAb) with or without platinum chemotherapy (pemetrexed/cisplatin/carboplatin/paclitaxel). Targets/pathways: mutant KRAS and downstream RAS–MAPK/PI3K signaling in tumor cells, upstream EGFR signaling, angiogenesis (VEGF), immune checkpoint PD-1/PD-L1 to activate T cells, and cytoskeleton/DNA synthesis and crosslinking in rapidly dividing tumor cells.