Nanoparticle polymeric micellar paclitaxel (pm-Pac), platinum, and sintilimab as first-line treatment for advanced or metastatic non-squamous non-small cell lung cancer: a phase II study

Nanoparticle polymeric micellar paclitaxel (pm-Pac), an optimized formulation of paclitaxel with improved pharmacokinetics and tumor-targeted delivery, showed clinical benefit with cisplatin for first-line advanced non-small-cell lung cancer (NSCLC). This study evaluated a novel chemotherapeutic agent, pm-Pac, plus platinum and sintilimab, as first-line treatment for advanced or metastatic non-squamous NSCLC. This single-arm phase II study (NCT05782426) included a safety run-in and efficacy evaluation stages. Patients (≥ 18 years) with stage IIIB–IV untreated advanced or metastatic non-squamous NSCLC received 4–6 cycles of pm-Pac (230 mg/m 2 for cycle 1; escalated to 300 mg/m 2 from cycle 2 if minimum neutrophils ≥ 1.0 × 10 9 /L, platelets ≥ 80 × 10 9 /L, and no grade 2–4 nonhematologic toxicity), carboplatin (AUC 5 mg/mL/min), and sintilimab (200 mg) intravenously every 3 weeks, followed by maintenance therapy with sintilimab or plus pm-Pac (≤ 230 mg/m 2 ) for up to 2 years or until disease progression, unacceptable toxicity, death, or initiation of new anti-tumor therapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. As of the data cutoff on January 28, 2026, 28 patients had received study treatment, of whom 11 (39.3%) had completed the protocol-specified 2-year treatment with sintilimab plus pm-Pac. With a median follow-up of 25.0 months, ORR and DCR were 78.6% and 89.3%, respectively. Median DoR reached 24.2 months. Median PFS was 18.2 months, with estimated PFS rates of 61.3% at 12 months and 43.8% at 24 months. OS remained immature. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 75.0% of patients. TEAEs led to treatment interruption in four patients and permanent discontinuation in seven patients. irAEs of grade ≥ 3 occurred in 32.1% of patients. One patient died from an immune-related grade 5 pneumonitis. The combination of pm-Pac, carboplatin, and sintilimab showed promising efficacy with manageable safety as first-line treatment for EGFR/ALK -negative advanced or metastatic non-squamous NSCLC regardless of programmed cell death ligand-1 expression, supporting further evaluation in randomized controlled trials. ClinicalTrials.Gov Identifier: NCT05782426. https://clinicaltrials.gov/study/NCT05782426 ).