Virtual Library
Start Your Search
Neal E. Ready
Author of
-
+
P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.01-02 - Long-Term Outcomes with First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 3-Year Follow-Up from CheckMate 012 (ID 12380)
16:45 - 18:00 | Author(s): Neal E. Ready
- Abstract
Background
CheckMate 012 (NCT01454102) is a phase 1 study evaluating several nivolumab monotherapy/combination regimens as first-line treatment for advanced non-small cell lung cancer (NSCLC). CheckMate 012 was the first study to suggest the benefit of nivolumab plus ipilimumab in NSCLC. In the phase 3 study CheckMate 227, nivolumab plus ipilimumab recently demonstrated significantly improved progression-free survival (PFS) as well as more frequent, deeper, and more durable responses versus chemotherapy in patients with chemotherapy-naive advanced NSCLC and high tumor mutational burden (TMB). Here, we provide 2-year follow-up results for nivolumab plus ipilimumab from CheckMate 012. Three-year results, the longest follow-up to date for an immuno-oncology combination in NSCLC, will be presented.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible patients had recurrent stage IIIb or stage IV chemotherapy-naive NSCLC and Eastern Cooperative Oncology Group performance status 0–1. Patients received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks (n=38) or every 6 weeks (n=39) until disease progression, unacceptable toxicity, or consent withdrawal; pooled results of these two cohorts are presented. Endpoints included safety/tolerability (primary); objective response rate and PFS (secondary); and overall survival (OS), chemotherapy-free survival (CFS), and efficacy by TMB status (exploratory).
4c3880bb027f159e801041b1021e88e8 Result
With 2 years of follow-up, no new safety signals were observed. Thirty-three of 77 patients (43%) achieved objective responses, including six investigator-assessed complete responses (8%), three of which were complete pathological responses. Responses were durable (median duration of response, not reached; range, 1.4+ to 27.9+ months). The 2-year PFS rate was 29%. At the time of database lock, 32 of 34 patients (94%) with OS ≥2 years were alive, with four (12%) remaining on treatment and progression-free; 14 (41%) were off treatment and progression-free without subsequent therapy. Three-year follow-up results to be presented include OS, PFS, and select data on CFS, efficacy by TMB status, and characteristics of long-term survivors.
8eea62084ca7e541d918e823422bd82e Conclusion
With long-term follow-up, nivolumab plus ipilimumab continued to demonstrate durable clinical benefit and a consistent safety profile as first-line treatment for patients with advanced NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53 -
+
P1.01-79 - CheckMate 817: Safety of Flat-Dose Nivolumab Plus Weight-Based Ipilimumab for the First-line (1L) Treatment of Advanced NSCLC (ID 12004)
16:45 - 18:00 | Author(s): Neal E. Ready
- Abstract
Background
CheckMate 227 demonstrated significant, clinically meaningful progression-free survival benefit with 1L nivolumab 3 mg/kg every 2 weeks (Q2W) plus low-dose ipilimumab 1 mg/kg Q6W vs chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and tumor mutational burden (TMB) ≥10 mutations/megabase. The dose and schedule for this combination regimen were optimized for 1L NSCLC in CheckMate 012 and further validated in CheckMate 568 and CheckMate 227. Flat dosing of nivolumab (240 mg Q2W) may simplify treatment while providing comparable exposure, and was recently approved for previously treated NSCLC. CheckMate 817 (NCT02869789) is a multi-cohort, open-label phase 3b/4 study evaluating the safety and efficacy of flat-dose nivolumab plus weight-based low-dose ipilimumab in recurrent/metastatic NSCLC. We report safety results from Cohort A, which evaluated this regimen in the 1L setting; updated results will be presented.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with ECOG PS ≤1 and previously untreated NSCLC were eligible, regardless of tumor programmed death ligand 1 (PD-L1) expression and TMB. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W were administered for 2 years or until disease progression/unacceptable toxicity. The primary endpoint was safety assessed by the incidence of grade ≥3 select treatment-related adverse events (TRAEs; defined as AEs of potential immunologic causes).
4c3880bb027f159e801041b1021e88e8 Result
Enrollment occurred between October 2016 and August 2017, with 391 patients initiating treatment at 68 academic and community-based centers in Europe and North America. Median age was 65 years and 27.9% of patients had squamous histology. PD-L1 expression was evaluable in 91% of patients; of these, 50% had ≥1% tumor PD-L1 expression. At database lock (March 1, 2018), minimum follow-up was 5.4 months and 34.5% of patients remained on treatment. The median (range) number of nivolumab and ipilimumab doses received were 9 (1–28) and 3 (1–10), respectively. Any grade and grade 3–4 TRAEs occurred in 74.4% and 27.6% of patients, respectively; 14.1% of patients discontinued treatment due to TRAEs. Rates of any grade select TRAEs by category ranged from 1.3% (renal) to 28.4% (skin). The most common grade 3–4 select TRAEs by category were hepatic (4.6%), pulmonary (3.1%), and gastrointestinal (3.1%). Two treatment-related deaths were reported; one due to Guillain-Barré syndrome and one due to rhabdomyolysis leading to heart failure.
8eea62084ca7e541d918e823422bd82e Conclusion
The safety profile of flat-dose nivolumab plus low-dose ipilimumab was consistent with previous reports of weight-based nivolumab plus low-dose ipilimumab optimized for NSCLC. Toxicities were manageable with no new safety signals identified.
6f8b794f3246b0c1e1780bb4d4d5dc53
