Induction therapy of pralsetinib followed by conversion surgery for unresectable locally advanced non-small cell lung cancer with the rearranged during transfection (RET) fusion gene mutation: protocol for a single-arm phase II prospective trial (the SALVAGE-P trial).

Background: Selective rearranged during transfection (RET) inhibitors have been approved as first-line treatment for locally advanced non-small cell lung cancer (NSCLC) harboring RET fusion gene mutations. Growing evidence shows that loco-regional therapy including salvage surgery may improve the prognosis of locally advanced NSCLC after induction therapy. Therefore, we initiated the SALVAGE-P trial to assess the safety and feasibility of induction selective RET inhibitors followed by conversion surgery in treating initially unresectable locally advanced NSCLC. Methods: This is a single-arm, phase II prospective study. Patients with treatment-naïve, unresectable locally advanced NSCLC (clinical stage IIIA, IIIB, and IIIC) harboring RET fusion gene mutations will be eligible for our study (N=25). Patients will receive induction therapy of pralsetinib (400 mg QD) for up to 6 months. If the primary tumor becomes resectable, participants will undergo surgical resection (lobectomy with systematic lymph node dissection). After surgery, participants will receive 4 cycles of pemetrexed (500 mg/m Discussion: The SALVAGE-P trial aims to assess the safety and feasibility of induction selective RET inhibitors followed by conversion surgery, which will begin in January 2026, with primary completion anticipated in December 2028. Trial Registration: This trial has been registered in the Chinese Clinical Trial Registry with a registration number of ChiCTR2600116415.