Low-dose Gemcitabine Combined With Nivolumab for Second-line and Above Line Treatment of NSCLC
Status:
Not yet recruiting
Trial end date:
2023-04-01
Target enrollment:
Participant gender:
Summary
In recent years, immunotherapy research has made great progress, especially the
immunocheckpoint inhibitors represented by anti-pd-1 antibody have shown good efficacy in the
treatment of malignant tumors, and some patients can achieve long-term survival. However,
despite the encouraging clinical data, only a small number of people have benefited.
Therefore, how to further improve the efficacy of immunotherapy and expand the benefit
population has become the focus of this field.
The applicant was previously published in Oncoimmunology (2017; E1331807) pointed out in the
above article: MDSC is a group of immunosuppressive cells, the number of this group of cells
in the body of cancer patients is more than normal, its presence affects the proliferation,
activation and function of T cells, is one of the important factors affecting the efficacy of
immunocheckpoint inhibitors. Therefore, ideal drugs used in combination with immunocheckpoint
inhibitors should meet the following conditions: first, they can kill or inactivate tumor
cells to release tumor-specific or associated antigens; Second, MDSC and other
immunosuppressive cells can be eliminated. Third, the number and function of T cells were not
affected.
Gemcitabine is a synthetic antimetabolic tumor drug widely used in the treatment of locally
advanced or metastatic non-small cell lung cancer. Myelosuppression is the dose - limiting
toxicity of gemcitabine, which includes lymphocytopenia. Therefore, if the commonly used
clinical dose gemcitabine is used in combination with pd-1 antibody, the effect of pd-1
antibody will be affected due to the reduction of lymphocytes caused by gemcitabine.
Therefore, we speculated that the reduced-dose treatment of gemcitabine combined with pd-1
antibody might have synergistic anti-tumor effect on the second-line and above second-line
treatment of non-small cell lung cancer with negative driver gene, and the adverse reactions
were relatively mild.
This study is a phase IV, open, non-randomized, single-arm, single-center study to
investigate the safety and efficacy of half-dose gemcitabine combined with pd-1 antibody in
second-line and above treatment of non-small cell lung cancer patients with negative driver
genes. Fifty subjects will be enrolled in this study. The primary endpoint of the study was
ORR, while secondary endpoints included DCR, PFS, and OS.