Combination of golidocitinib (a JAK1 inhibitor) with anti–PD-1 antibody to improve tumor response and patient quality of life: Preliminary results from an ongoing JACKPOT 33 study.

Abstract

8555 Background: Chemo-immunotherapy remains the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver mutations. Unfortunately, treatment resistance is inevitable. Janus kinase (JAK) inhibition may improve the efficacy of immunotherapy by pivoting T cell exhaustion dynamics, enhancing and extending patient response. Herein, we report the anti-tumor efficacy and safety data from an ongoing phase 2 study (NCT06198907, JACKPOT33) evaluating golidocitinib, a JAK1-specific inhibitor, combined with sintilimab, an anti-PD-1 antibody, as first-line treatment in patients with PD-L1 positive advanced NSCLC without driver mutations. Methods: Eligible patients with advanced NSCLC with PD-L1 TPS ≥ 1% were enrolled in the study. Patients received two cycles of chemo-immunotherapy only, followed by golidocitinib 150 mg orally once daily plus sintilimab 200 mg intravenous every 3 weeks until disease progression, intolerance, up to 2 years of treatment, or other discontinuation criteria were met. The primary objective was to evaluate the anti-tumor efficacy, and the secondary objectives included safety and tolerability. Results: As of December 23, 2025, a total of 47 patients were enrolled in the JACKPOT33 study. The median age of these patients was 63 years, with 87.2% males, 61.7% with non-squamous histology, 40.4% with PD-L1 high (TPS ≥50%) and 59.6% with PD-L1 low (TPS 1-49%) expression. Most (74.5%) of the patients had metastatic disease at baseline, with 8.5% having brain metastasis. Per investigator assessment, the overall response rate (ORR) after two cycles of chemo-immunotherapy was 42.6%. Following the addition of golidocitinib with sintilimab, deeper tumor shrinkage and additional responders were observed, resulting in an ORR of 63.8% (30/47). The improvement in ORR with golidocitinib was most profound in patients with high PD-L1 levels, with rates of 84.2% vs. 50% in the high and low expression cohorts, respectively. No difference in ORR was observed between patients with squamous or non-squamous carcinoma (61.1% vs 65.5%). As of the data cut-off date, 32 out of 47 patients remained on treatment and benefiting. The longest treatment duration reached 15.9 months. The combination of golidocitinib and sintilimab was well tolerated. The incidence of immune-related adverse effects was markedly decreased, and patients' self-reported quality of life significantly improved. No new safety signal was observed. Conclusions: In treatment-naïve patients with advanced NSCLC, golidocitinib plus sintilimab following chemo-immunotherapy demonstrated encouraging and durable anti-tumor efficacy, particularly in those with high PD-L1 expression. A profound decrease in immune-related adverse effects was observed. Updated data will be presented at the conference. Clinical trial information: NCT06198907 .