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.

9560 Background: In Part 1 of the phase II CheckMate 568 study (NCT02659059), NIVO + IPI was active and tolerable in patients (pts) with advanced NSCLC. The addition of chemo to dual immune checkpoint inhibitor therapy may further improve initial disease control. We report results from Part 2 of CheckMate 568, which evaluates NIVO + IPI combined with 2 cycles of chemo in pts with advanced treatment-naive NSCLC. Methods: Adult pts with untreated stage IV NSCLC received NIVO 360 mg Q3W + IPI 1 mg/kg Q6W combined with 2 cycles of histology-based platinum-doublet chemo, followed by NIVO + IPI without chemo until disease progression/unacceptable toxicity for ≤ 2 years. The primary endpoints were dose-limiting toxicity (DLT) within the first 9 weeks and safety/tolerability. Treatment was considered safe if ≤ 25% of at least 22 evaluable pts 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. Results: In total, 36 pts received treatment; 97% of pts completed 2 cycles of chemo combined with NIVO + IPI. Three pts discontinued IPI while continuing NIVO. Minimum follow-up was 14.9 months. Only 1 (3%) pt experienced a DLT (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 IPI, delay of NIVO, and treatment with prednisone; chemo was continued throughout and NIVO was restarted thereafter without recurrent toxicity. Grade 3–4 TRAEs occurred in 21 (58%) pts. Eight (22%) pts experienced a TRAE leading to discontinuation, most commonly colitis, encephalopathy, pneumonitis, and arthralgia (each in 2 [6%] pts); 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%] pts); the most common grade 3–4 select TRAEs were endocrine (3 [8%] pts), skin related, gastrointestinal, and pulmonary (each in 2 [6%] pts). No treatment-related deaths occurred. Updated safety in addition to efficacy data will be presented. Conclusions: In pts with untreated advanced NSCLC, the addition of 2 cycles of platinum-doublet chemo to NIVO + tumor-optimized IPI was tolerable. No unexpected safety signals were observed. Clinical trial information: NCT02659059 .