In Part 1 of the phase II CheckMate 568 study, Nivolumab ( Opdivo ) plus Ipilimumab ( Yervoy ) was active and tolerable in patients with advanced non-small cell lung cancer ( NSCLC ).
The addition of chemo to dual immune checkpoint inhibitor therapy may further improve initial disease control.
Researchers have reported results from Part 2 of CheckMate 568, which is evaluating Nivolumab + Ipilimumab combined with 2 cycles of chemo in patients with advanced treatment-naive NSCLC.
Adult patients with untreated stage IV NSCLC received Nivolumab 360 mg Q3W + Ipilimumab 1 mg/kg Q6W combined with 2 cycles of histology-based Platinum-doublet chemo, followed by Nivolumab + Ipilimumab without chemo until disease progression / unacceptable toxicity for 2 years or less.
The primary endpoints were dose-limiting toxicity ( DLT ) within the first 9 weeks and safety / tolerability.
Treatment was considered safe if less than or equal to 25% of at least 22 evaluable patients had a dose-limiting toxicity.
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; 97% of patients completed 2 cycles of chemo combined with Nivolumab + Ipilimumab.
Three patients discontinued Ipilimumab while continuing Nivolumab.
Minimum follow-up was 14.9 months.
Only 1 ( 3% ) patient experienced a dose-limiting toxicity ( transient, asymptomatic grade 3 AST and ALT elevation ) within the first 9 weeks.
The elevation occurred on cycle 1, day 21 and resolved 2 weeks later with discontinuation of Ipilimumab, delay of Nivolumab, and treatment with Prednisone; chemo was continued throughout and Nivolumab was restarted thereafter without recurrent toxicity.
Grade 3–4 TRAEs occurred in 21 ( 58% ) patients. Eight ( 22% ) patients experienced a TRAE leading to discontinuation, most commonly colitis, encephalopathy, pneumonitis, and arthralgia ( each in 2 [ 6% ] patients ); these events occurred outside of the 9-week window for DLT assessment.
The most common select TRAEs ( defined as AEs of potential immunologic causes ) were skin related ( 18 [ 50% ] patients ); the most common grade 3–4 select TRAEs were endocrine ( 3 [ 8% ] patients ), skin related, gastrointestinal, and pulmonary ( each in 2 [ 6% ] patients ).
No treatment-related deaths occurred.
In conclusion, in patients with untreated advanced NSCLC, the addition of 2 cycles of Platinum-doublet chemo to Nivolumab + tumor-optimized Ipilimumab was tolerable.
No unexpected safety signals were observed. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020