In Part 1 of the phase 2 CheckMate-568 study, nivolumab (NIVO) combined with ipilimumab (IPI) was shown to be active and tolerable in patients with advanced non–small-cell lung cancer (NSCLC). Researchers hypothesized that the addition of chemotherapy to dual immune checkpoint inhibitor therapy can further improve initial disease control. Part 2 of CheckMate-568 evaluated NIVO + IPI combined with 2 cycles of chemotherapy in patients with advanced treatment-naive NSCLC.
In Part 2 of CheckMate-568, adult patients with untreated stage IV NSCLC received NIVO (360 mg every 3 weeks) and IPI (1 mg/kg every 6 weeks) combined with 2 cycles of histology-based platinum-doublet chemotherapy. This treatment was followed by NIVO + IPI (without chemotherapy) until disease progression or unacceptable toxicity for up to 2 years.
The primary end points of this study were dose-limiting toxicity (DLT) within the first 9 weeks, safety, and tolerability. Treatment was considered safe if ≤25% of at least 22 evaluable patients had a DLT. DLTs included, but were not limited to, uncontrolled grade 3 non-skin treatment-related adverse events (TRAEs), grade 4 TRAEs, grade 2 treatment-related pneumonitis not resolved within 14 days, and treatment-related hepatic function abnormalities.
In total, 36 patients received treatment, with most (97%) completing 2 cycles of chemotherapy combined with NIVO + IPI. Three patients discontinued IPI while continuing treatment with NIVO. After minimum follow-up of 26 months, only 1 (3%) patient experienced a DLT within the first 9 weeks: transient, asymptomatic grade 3 AST and ALT elevation.
Grade 3/4 TRAEs occurred in 75% of patients; 25% of patients experienced a TRAE that led to discontinuation. These events included colitis, encephalopathy, pneumonitis, and arthralgia. These TRAEs occurred outside of the 9-week window for DLT assessment.
The most common select TRAEs, defined as adverse events of potential immunologic causes, were skin-related and occurred in 50% of patients (any grade). The most common grade 3/4 select TRAEs were endocrine (3 patients, 8%), skin-related, gastrointestinal, and pulmonary (each in 2 patients, 6%). No treatment-related deaths occurred.
Addition of 2 cycles of platinum-doublet chemotherapy to NIVO + IPI showed encouraging clinical activity. The disease control rate was 89%, and the overall response rate was 47%. Median progression-free survival was 10.8 months, and median overall survival was 19.4 months. Thirteen of 36 patients were alive after a minimum follow-up of 26 months.
Researchers concluded that, in patients with untreated advanced NSCLC, addition of 2 cycles of platinum-doublet chemotherapy to NIVO + IPI is effective and tolerable with no unexpected safety signals. A phase 3 study, CheckMate-9LA, is also evaluating this combination regimen.
- Gainor JF, Schneider JG, Gutierrez M, et al. Nivolumab (NIVO) plus ipilimumab (IPI) with two cycles of chemotherapy (chemo) in first-line metastatic non-small cell lung cancer (NSCLC): CheckMate 568 Part 2. J Clin Oncol. 2020;38:suppl (abstract 9560).