1. Combination therapy of nivolumab and ipilimumab achieved rapid and deep tumor regression in a subset of metastatic melanoma patients.
2. The therapy is associated with significant side effects that are comparable to monotherapies.
Evidence Rating Level: 2 (Good)
Study Rundown: This study suggests that combination therapy involving multiple immune checkpoint blockers may prove effective against metastatic melanoma. The rationale is that immune checkpoint blockers may further sensitize immune cells to the presence of cancer cells. Subject to the limitations of a phase 1 trial, the study shows encouraging efficacy and tumor response rate with more than half of the patients achieving tumor reduction of at least 80%. The adverse effects were comparable to previously established monotherapy with either agent alone.
In-Depth [phase 1 clinical study]: As a phase 1 trial, the study focused on drug safety and dose-ranging. The trial assigned 86 patients to 2 cohorts. The concurrent regimen cohort (size = 53) received IV nivolumab and ipilimumab q3w for 4 doses, followed by nivolumab q3w for 4 doses. The sequenced regimen cohort (size = 33) received nivolumab q2w for up to 48 doses following prior ipilimumab treatments.
The concurrent regimen cohort had treatment-related adverse event rate of 93%, grade 3 or 4 treatment-related event rate of 53%, and serious treatment-related event rate of 49%. This compares to 73%, 18%, and 21% in the sequenced regimen cohort (size = 33), respectively. Maximum dose was identified as nivolumab 1 mg/kg and ipilimumab 3 mg/kg. Treatment-related adverse events were generally reversible and manageable with immunosuppression.
In the concurrent regimen group, overall evidence of clinical activity reached 65%. 16 patients had tumor reduction of 80% or more at 12 weeks, 5 had complete response. The sequence regimen had clinical activity in 43%. 4 patients had tumor reduction of 80% or more at 8 weeks.
By Xiaozhou Liu and Mitalee Patil
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