Nivolumab After Cyclophosphamide and Doxorubicin Induction Therapy in NSCLC With PD-L1<10%
Status:
Recruiting
Trial end date:
2022-05-31
Target enrollment:
Participant gender:
Summary
Nivolumab is now the standard of care for second-line treatment of advanced squamous or
nonsquamous NSCLC regardless of the tumor's expression of PD-1L. CheckMate057 trial results
showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had
stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab
produced significantly better overall survival during follow-up as long as 18 months,
compared with a docetaxel-based regimen. But during the first 3 months on randomized
treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly
reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on
nivolumab. A post hoc analysis showed a trend to a higher risk for death during the first 3
months of nivolumab treatment among patients with poorer prognostic features, more aggressive
disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients
benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1
expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to
anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment
with low dose chemotherapy.
Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and
doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with
cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.