Dizal Pharmaceuticals has announced promising clinical findings for golidocitinib, a first-in-class Janus kinase 1 (JAK1) inhibitor, when combined with PD-1 antibodies in non-small cell lung cancer (NSCLC) patients whose disease progressed after prior anti-PD-1 therapy.
According to data from an exploratory Phase 1b study with a cutoff date of August 31, 2023, the combination therapy demonstrated an objective response rate (ORR) of 44.3%. Notably, more than half of patients who experienced tumor remission achieved a complete response, with a complete response rate of 23.9%. The median duration of response was 20.7 months.
"Immunotherapy alone or with chemotherapy is commonly used as front line treatment for NSCLC patients without driver mutations. Unfortunately, resistance is inevitable and once the disease progresses, the prognosis is poor and treatment option is limited," said Xiaolin Zhang, PhD, CEO of Dizal. "The findings we are presenting at ELCC 2025 highlight the potential for golidocitinib-based combination regimen to delay or overcome the resistance. The preliminary results are very promising and justify further clinical validation."
Mechanism of Action and Scientific Rationale
Recent studies have identified dysregulated activation of the JAK/STAT pathway as a significant contributor to resistance against immune checkpoint inhibitors in cancer immunotherapy. This pathway leads to prolonged release of interferon-gamma (IFN-γ), which can paradoxically inhibit anti-tumor immune responses over time.
Golidocitinib works by selectively inhibiting JAK1, potentially blocking the formation of cancer growths through inhibition of cellular proliferation in JAK1-overexpressing tumor cells. Preclinical studies have demonstrated that combining golidocitinib with PD-1 antibodies produces synergistic anti-tumor effects, providing a strong scientific rationale for the clinical investigation.
Study Design and Patient Population
The ongoing exploratory Phase 1b clinical study is designed to enroll 30 patients with locally advanced or metastatic NSCLC who have previously received either anti-PD-1 monotherapy or anti-PD-1 therapy with platinum-containing chemotherapy. Complete details of the trial design and updated clinical results will be presented at the 2025 European Lung Cancer Congress (ELCC) in Paris on March 26-29.
Regulatory Status and Development Pipeline
Golidocitinib has already received regulatory approval in China for the treatment of relapsed/refractory peripheral T-cell lymphoma (r/r PTCL). In February 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to golidocitinib for r/r PTCL, a process designed to expedite the development and review of drugs addressing serious conditions with unmet medical needs.
The GOLDEN trial, currently being conducted at The University of Texas MD Anderson Cancer Center in Houston, is investigating golidocitinib with or without CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with PTCL.
Additional Pipeline Developments
In addition to the golidocitinib combination therapy, Dizal will also present positive results from a Phase II study of sunvozertinib in combination with anlotinib at ELCC 2025. This combination demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who had failed prior EGFR-TKI therapies, with an objective response rate of 33.3% and a disease control rate of 100% as of December 25, 2024.
Clinical Significance
The findings for golidocitinib are particularly significant given the limited treatment options for NSCLC patients who develop resistance to immunotherapy. The high response rate and notably long duration of response suggest this combination approach could represent an important advancement in addressing immunotherapy resistance, a major challenge in lung cancer treatment.
If confirmed in larger studies, this therapeutic approach could potentially change treatment paradigms for patients with immunotherapy-resistant NSCLC, offering new hope for those with limited options after progression on standard therapies.
