PD-L1 can predict benefit from anti-PD-1/L1 therapies; TMB is an emerging biomarker that may have additional predictive utility. We compared the utility of high TMB and PD-L1 to predict outcomes in NSCLC non-squamous pts treated with anti-PD-L1 (durvalumab) and anti-CTLA-4 monoclonal antibodies (tremelimumab, D+T).
NCT02000947 was a ph 1b study in advanced NSCLC; this exploratory study focused on a cohort of IO-naive non-squamous NSCLC who progressed after 1 prior platinum-based therapy. Pts were treated with D 20 mg/kg Q4W up to 12 months and T 1 mg/kg Q4W with the first 4 cycles of D. By 20 OCT 2017, 214 pts received D+T. DNA sequencing was conducted with the FoundationOne CDxTM on 106 tumors and IHC was performed on tumoral PD-L1 on 193 biopsies using the validated SP263 Ventana assay, all of sufficient quality. NSCLC with ≥25% tumor cells stained for PD-L1 at any intensity were PD-L1+ and high TMB was the top tertile of nonsynonymous mutations per Mb (11.41). KM, Cox PH models and Spearman’s rho were calculated; RECIST v1.1 was used for response.
Of 200 biopsies evaluated for TMB, 106 (53%) provided usable data. PD-L1 was modestly correlated with TMB (r = 0.3, p = 0.002). PD-L1+ pts had higher ORR, PFS and OS compared to PD-L1-. TMB high pts had higher PFS than TMB low. HRs for PD-L1+ and TMB high were similar. TMB high/PD-L1+ pts did not have substantially better ORR than single positive pts, and TMB low/PD-L1- had the lowest response.Table: 65PD
|# Pts (# events [PFS])||ORR % (95% CI)||Median PFS, mo (95% CI)||PFS HR (95% CI); p|
|TMB high||37 (27)||29.7%||7.1 (1.7,9.1)||0.60 (0.38,0.96); 0.032|
|TMB low||69 (59)||10.1%||1.7 (1.6,3.6)|
|PD-L1+||57 (39)||35.1%||7.1 (3.5,9.2)||0.55 (0.38,0.80); 0.0018|
|PD-L1-||136 (114)||11.8%||3.3 (1.7,3.6)|
The predictive utility of TMB was similar to that of PD-L1 in this cohort of NSCLC pts treated with D+T. This abstract was withdrawn from ASCO.
Clinical trial identification
Legal entity responsible for the study
B.W. Higgs, C.A. Morehouse, P.Z. Brohawn, S. Sridhar, R. Raja, G. Gao, J. Englert, K. Ranade: Employment: Medimmune/AstraZeneca; Stock ownership: AstraZeneca.