Pre-clinical studies indicated that arginine-deprivation therapy using pegylated arginine deiminase may be effective in patients with ASS1-deficient small-cell lung cancer. Therefore to study arginine-deprivation therapy using pegylated arginine deiminase may be effective in patients with ASS1-deficient small-cell lung cancer this research was done.
Patients received weekly intramuscular pegargiminase, until unacceptable toxicity or disease progression. The primary endpoint was tumor response assessed by Response Evaluation Criteria in Solid Tumors with secondary endpoints including tolerability, pharmacodynamics, and immunogenicity.
22 patients were enrolled that fulfilled the eligibility criteria for the study: 9 in the sensitive disease cohort and 13 in the refractory disease cohort. At a pre-planned interim analysis, the best overall response observed was stable disease in 2 patients in each cohort. Owing to the lack of response and slow accrual in the sensitive disease cohort, the study was terminated early. Pegargiminase treatment was well-tolerated with no unexpected adverse events or discontinuations.
The study concluded that although pegargiminase monotherapy in SCLC failed to meet its primary endpoint of RECIST-confirmed responses, more recent molecular stratification, including MYC status, may provide new opportunities moving forward.