Category: Professional Posters
Purpose: Data are limited for immunotherapy in patients with advanced NSCLC and poor performance status or other comorbidities. CheckMate 817 is a multi-cohort, open-label phase 3b/4 study investigating safety and efficacy of flat-dose nivolumab plus weight-based low-dose ipilimumab in advanced NSCLC. Here we evaluate this regimen as first-line treatment in special populations (cohort A1) and a reference population (cohort A; previously reported in Paz-Ares L, et al. WCLC 2018).
Methods: Patients with previously untreated advanced NSCLC in Cohort A1 (n=198) had ECOG PS 2 or ECOG PS 0–1 with 1 of: asymptomatic untreated brain metastases, hepatic or renal impairment, or HIV; Cohort A (n=391) had ECOG PS 0–1. Cohort A1 patients were grouped as ECOG PS 2 (PS2 [n=139]) and all other special populations (AOSP [n=59]); AOSP included patients with brain metastases (n=44), renal impairment (n=8), hepatic impairment (n=4), or HIV (n=4). Patients with known EGFR mutations or ALK translocations sensitive to available targeted therapy were excluded from both cohorts. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W was administered for two years or until disease progression/unacceptable toxicity. Safety and efficacy endpoints were assessed; Cohort A1 analyses were exploratory.
Results: Median follow-up was 9.1 and 11.3 months in Cohorts A1 and A, respectively. Baseline characteristics were generally balanced between cohorts. In Cohort A1, rates of any grade/grade 3–4 treatment-related adverse events (TRAEs) were 67%/27%, respectively, 62%/24% in PS2 and 78%/34% in AOSP. In Cohort A, they were 75%/31%, respectively. Rates of any grade/grade 3–4 TRAEs leading to discontinuation in Cohort A1, PS2, and AOSP were 15%/12%, 14%/12%, and 17%/12%, respectively, and 18%/13% in Cohort A. Two treatment-related deaths occurred in Cohort A1 (interstitial diffuse pneumonitis [n=1] and polymyositis [n=1]; both in PS2) and 2 occurred in Cohort A (grade 5 cardiac failure secondary to immune-mediated grade 3 rhabdomyolysis of heart and other muscles [n=1]; Guillain–Barré syndrome [n=1]). ORR (95% CI) in cohort A1, PS2, and AOSP was 25% (19.4–31.9), 20% (13.8–27.8), and 37% (25.0–50.9), respectively, and in Cohort A was 35% (30.1–39.7). Median PFS (95% CI) in cohort A1, PS2, and AOSP was 3.9 (2.8–5.4), 3.6 (2.8–5.4), and 4.2 (2.6–9.6) months, respectively, and in Cohort A was 6.0 (4.7–8.1) months. In both cohorts, TMB ≥10 mut/Mb and PD-L1 expression ≥1% or ≥50% were associated with numerically longer median PFS.
Conclusion: First-line flat-dose nivolumab plus weight-based ipilimumab showed a consistent safety profile in special populations with advanced NSCLC, including those with ECOG PS 2. Patients with either high TMB or higher tumor PD-L1 expression appeared to exhibit improved efficacy.