P1.01-61 A Phase II Umbrella Study of Camrelizumab in Different PD-L1 Expression Cohorts in Pre-Treated Advanced/Metastatic Non-Small Cell Lung Cancer

Abstract

The role of PD-L1 expression in 2nd line and beyond non-small cell lung cancer (NSCLC) remains controversial. Camrelizumab (SHR-1210) is a potent anti-PD-1 monoclonal antibody and has shown promising activity in NSCLC in Phase I studies. We report results from the SHR-1210-201 study (NCT03085069), a phase II umbrella study of camrelizumab monotherapy in different PD-L1 expression cohorts in Chinese patients with previously treated advanced or metastatic NSCLC. Patients who progressed during or following platinum-based doublet chemotherapy were enrolled and assigned to one of 4 cohorts based on PD-L1 expression. Patients with EGFR or ALK genomic alterations were eligible provided they had disease progression with at least one approved tyrosine kinase inhibitor and with ≥50% PD-L1 expression in tumor. All enrolled patients received camrelizumab at 200 mg IV Q2W until loss of clinical benefit. The primary endpoint was objective response rate (ORR), other endpoints included progression-free survival (PFS) and overall survival (OS). As of Aug 1st 2018, of all the 259 patients who underwent screen, 229 cases could be pathologically evaluated. PD-L1 expression were 47.6% (109/229) in PD-L1 < 1%, 27.1% (62/229) in PD-L1 ≥1-<25%, 8.7% (20/229) in ≥25-<50% and 16.6% (38/229) in ≥50%. A total of 63.8% (146/229) patients were enrolled. 89.0% of patients had stage IV NSCLC and 54.8% had non-squamous tumor histology. ORR was 18.5% (95%CI: 12.6%–25.8%) in ITT population. Subgroup analysis showed increased PD-L1 expression was associated with better response rate (Table 1). No response was observed in patients with EGFR mutation. The responders had durable response (median: 15.1 months; 95%CI: 5.5–not reached). Median PFS was 3.2 months (95%CI: 2.0–3.4) and median OS was 19.4 months (95%CI: 11.6–not reached) (Table 1). Treatment-related adverse events (AEs) occurred in 87.7% of patients (all Grade); 20.5% had ≥G3 related AE; and 15.8% had related SAE. 21.2% of AEs led to dose interruption and 7.5% led to treatment discontinuation.Table 1Efficacy data in subgroupsPopulationNo of ptsORR, % (95%CI)PFS (month), median (95%CI)1YOS, % (95%CI)OS (month), median (95%CI)PD-L1<1%7412.2% (5.7%, 21.8%)2.1 (1.9, 3.2)47.1% (33.8%, 59.2%)11.6 (7.8, NR)PD-L1 ≥1% and < 25%3119.4% (7.5%, 37.5%)3.1 (1.8, 4.9)76.7% (57.2%, 88.2%)NR (NR, NR)PD-L1 ≥25% and < 50%1145.5% (16.7%, 76.6%)6.0 (1.9, NR)81.8% (44.7%, 95.1%)NR (2.9, NR)PD-L1 ≥50% (without EGFR mutation)2528.0% (12.1%, 49.4%)7.6 (3.3, 11.4)55.2% (32.3%, 73.2%)NR (8.6, NR)PD-L1 ≥50% (with EGFR mutation)501.7 (1.2, NR)40.0% (5.2%, 75.3%)10.3 (1.2, NR)ITT14618.5% (12.6%, 25.8%)3.2 (2.0, 3.4)56.6% (47.3%, 64.9%)19.4 (11.6, NR)Abbreviation: NR, Not Reached. Open table in a new tab Abbreviation: NR, Not Reached. In Chinese patients with previously treated advanced/metastatic NSCLC, camrelizumab demonstrated improved ORR, PFS, and OS compared with historical data of the 2nd line chemotherapy. The efficacy in patients with PD-L1 <1% is similar as the 2nd line mono-chemotherapy, while patients with higher PD-L1 expression derived greater benefit from camrelizumab, the ORR, PFS and OS in patients with PD-L1 ≥25% was comparable to the 1st line doublet chemotherapy in advanced NSCLC. Camrelizumab was well tolerated. This phase 2 data warrant further clinical studies of camrelizumab in NSCLC.