Therapy selection for previously treated patients with advanced NSCLC is evolving. ABOUND.2L+ evaluated safety and efficacy of nab-P monotherapy, nab-P + the epigenetic modifying agent CC-486, and nab-P + the PD-L1 inhibitor durvalumab.
Patients with advanced nonsquamous NSCLC and ≤ 1 prior chemotherapy were randomized to nab-P 100 mg/m2 on days 8 and 15 + CC-486 200 mg QD on days 1-14 or nab-P alone 100 mg/m2 on days 1 and 8, both administered q3w. The protocol was amended to include a nab-P + durvalumab arm (nab-P 100 mg/m2 on days 1 and 8 + durvalumab 1125 mg on day 15, q3w), which began enrolling after the other arms had completed enrollment and allowed the inclusion of patients with squamous histology or prior immunotherapy treatment. For all patients, treatment continued until unacceptable toxicity or tumor progression.
A total of 240 patients were enrolled. In the nab-P + CC-486 and nab-P arms, the median number of cycles was 4 and the median cumulative dose of nab-P was 600 and 800 mg/m2, respectively. Grade 3 or 4 (G3/4) treatment-emergent adverse events (AEs) were 59.5% and 54.4%, respectively. The most frequent hematologic G3/4 AEs were neutropenia (16.5% vs 10.1%) and anemia (1.3% vs 7.6%). G3/4 peripheral neuropathy occurred in 2.5% vs 7.6% of patients (nab-P + CC-486 vs nab-P). Adding CC-486 to nab-P did not result in improvements in PFS, OS, ORR, or DCR (Table). Preliminary data for 79 patients in the nab-P + durvalumab arm showed a median PFS of 4.4 months, median OS not estimable, a 20% ORR, and a 71% DCR. No new safety signals were identified.
|nab-P + CC-486 n = 81||nab-P n = 80|
|Median PFS, months||3.2||4.2|
|HR (95% CI)||1.3 (0.9 - 2.0)|
|Median OS, months||8.4||12.7|
|HR (95% CI)||1.4 (0.88 - 2.31)|
|ORR, n (%)a||11 (13.6)||11 (13.8)|
|Response rate ratio (95% CI)||0.99 (0.45 - 2.15)|
|Complete response Partial response Stable disease Progressive disease DCR (≥ stable disease)||0 11 (13.6) 41 (50.6) 22 (27.2) 52 (64.2)||0 11 (13.8) 43 (53.8) 19 (23.8) 54 (67.5)|
DCR, disease control rate; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.a
Response rate was based on the intent-to-treat population; however, 14 patients did not have a response assessment.
Single-agent nab-P is promising in previously treated nonsquamous NSCLC; addition of CC-486 did not appear to benefit patients clinically. Updated data for the ongoing durvalumab combination arm of the study will be presented. NCT02250326.
Clinical trial identification
Legal entity responsible for the study
D. Morgensztern: Consultant: Celgene, Abbvie and Bristol-Myers Squibb. T.J. Ong, J. Weaver: Full-time employee: Celgene Corporation. P.E. Postmus: Advisory Board: Advisory board Celgene, AstraZeneca, Roche, BMS, BI, Janssen, MSD, Clovis. C. Lewanski: Advisory Board Member: Eli Lilly. J. Bennouna: Advisory Board: Roche, Boehringer-Ingelheim, Astra-Zeneca, BMS; Honoraria: Roche, Boehringer-Ingelheim, Astra-Zeneca, BMS. J.R. Fischer: Employment: Klinik Löwenstein; Advisory Board: Astra Zeneca, BMS, Celgene, Roche, MSD, Boehringer; Consultant: Celgene; Speaker’s Bureau: Astra Zeneca, Celgene, Roche, BMS; Honoraria: Astra Zeneca, BMS, Celgene, Roche, MSD, Boehringer. D.J. Stewart: Grants/Research Support Recipient: Clinical trials support: Celgene, Boehringer Ingelheim, Astra Zeneca, Novartis, Bristol-Myers Squibb; Advisory Board: Roche Canada; Pfizer Canada; Boehringer Ingleheim Canada, Amgen, Novartis Canada. A. Ardizoni: Honoraria from Eli-Lilly, BMS, MSD, Boehringer. M. Wolfsteiner: Employment: FTE at PRA Health Sciences, contracted for Celgene (current). D. Talbot: Honoraria - Pfizer; Pierre Fabre Consulting or Advisory Role - Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Lilly; Novartis; Pfizer; Roche Travel, Accommodations, Expenses - Bristol-Myers Squibb; Ipsen; Lilly; Merck Sharp & Dohme; Novartis. R. Govindan: Honoraria - Boehringer Ingelheim Consulting or Advisory Role - Abbvie; Bayer; Boehringer Ingelheim; Celgene; Clovis Oncology; Genentech/Roche; GlaxoSmithKline; Helsinn Therapeutics; Novartis Research Funding - Abbvie (Inst); Bayer (Inst); GlaxoSmithKline (Inst); MethylGene (Inst) Travel, Accommodations, Expenses - Amgen; Boehringer Ingelheim; Celgene; Genentech; GlaxoSmithKline; Merck All other authors have declared no conflicts of interest.