Background: The pm-paclitaxel formulation for injection (pm-Pac), a novel drug delivery system composed of nanoparticle-encapsulated paclitaxel micelles, combined with cisplatin has been proven to improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC). But the efficacy and safety of pm-Pac in addition to PD-1/PD-L1 inhibitors had never been reported before. Methods: Treatment-naive, stage IIIB/IV Sq-NSCLC patients with ECOG PS 0-2(≤1, 91.1%) were eligible. Participants were given intravenous Tislelizumab (200mg, d1) plus pm-Pac (230 mg/m², d1) and carboplatin (AUC 5, d1), every 3 weeks until progression or unacceptable toxicity, with local radiotherapy or surgery allowed if treatment needed. The primary endpoints were ORR and safety. The secondary endpoints include DCR, PFS, and OS. AEs were graded according to CTCAE v5.0. Results: From Nov 2021 to Dec 2022, 45 patients were enrolled. The median age was 68 years (range 41-84), and most were male (93%) and former/current smokers (87%). 3 patients had baseline brain metastases and 31 patients had baseline PD-L1 evaluated. Twenty-two patients (48.9%) received subsequent local treatment because of the stable efficacy, including 18 radiotherapy and 4 surgery. Among all, 2 achieved confirmed CR, 36 achieved PR, 7 achieved SD, ORR was 84.4% and DCR was 100%. PFS and OS were immature. Kaplan-Meier survival analysis indicated that the 6m-PFS rate was 94.8% (95%CI:89.8%，97.6%), and a total of 41 (91.1%) patients are still alive on 1L treatment at the last follow-up on Feb 2023.The most common TRAE were alopecia (91.1%), leukopenia (80%), peripheral neurosensory numbness (55.6%) and extremity pain (24.4%). The most common grade 3 or higher AE was neutropenia (33.3%), which is commonly associated with chemotherapy. Conclusions: This is the first report about the new chemo-drug pm-Pac plus PD-1 inhibitor regimen that significantly improved ORR for advanced Sq-NSCLC with a tolerable safety profile, supporting further development of this new combination in the first-line treatment. Response rates.

Keywords: Pm-paclitaxel, PD-1 inhibitor, Advanced Sq-NSCLC.