The Phase III IMpower110 study (NCT02409342) is evaluating atezo (anti–PD-L1) monotherapy as 1L treatment (tx) in PD-L1–selected patients (pts) with NSCLC independent of tumour histology. IMpower110 met its primary endpoint with significant OS improvement in PD-L1–high (TC3 or IC3; ≥ 50% tumour cell [TC] or ≥ 10% tumour-infiltrating immune cell [IC]; VENTANA SP142 IHC assay) wild-type (WT; EGFR/ALK-negative) pts (HR, 0.59 [95% CI: 0.40, 0.89]; P = 0.0106). Efficacy analyses in prespecified biomarker subgroups by the SP263 and 22C3 PD-L1 IHC assays and bTMB are reported.
IMpower110 enrolled 572 chemo-naive pts with stage IV NSCLC, PD-L1 ≥ 1% TC or IC (TC1/2/3 or IC1/2/3; SP142), measurable disease by RECIST 1.1 and ECOG PS 0-1. Pts were randomised 1:1 to receive atezo 1200 mg IV q3w or platinum-based chemo (4 or 6 21-day cycles). OS (primary endpoint) was tested hierarchically in WT pts. Additional analyses included OS and PFS in the SP263 and 22C3 PD-L1 IHC and bTMB populations. PD-L1 cutoffs of ≥ 1% and ≥ 50% tumour proportion score (TPS) for 22C3 and ≥ 1% and ≥ 50% TC for SP263 were evaluated; bTMB cutoffs were ≥10, ≥ 16 and ≥ 20.
Biomarker-evaluable populations (BEP) in the TC1/2/3 or IC1/2/3 WT population (SP142; 554) included 534 (22C3), 546 (SP263) and 389 (bTMB) pts. Baseline characteristics in the IHC and bTMB BEP subgroups were generally balanced. OS and PFS in the PD-L1–high (TC3 or IC3; ≥ 50% TPS; ≥ 50% TC) subgroups favoured atezo (OS data shown in table). Stepwise OS and PFS improvement, favouring atezo, was seen up to bTMB ≥ 16; no further benefit was seen at ≥ 20.
Pt subgroups defined as PD-L1–high by all 3 IHC assays (SP142, 22C3, SP263) had similar OS and PFS benefit with atezo, despite the different assay sensitivities and scoring algorithms. Enrichment in clinical benefit, favouring atezo, was also seen in bTMB positive subgroups. Atezo monotherapy is a potential new 1L tx option for pts with PD-L1–high NSCLC.
| Subgroup | Median OS | HRa | |||
|---|---|---|---|---|---|
| Atezo | Chemo | ||||
| n | mo | n | mo | ||
| VENTANA SP142 (n = 554) | |||||
| TC1/2/3 or IC1/2/3 WT | 277 | 17.5 | 277 | 14.1 | 0.83 |
| TC3 or IC3 WT | 107 | 20.2 | 98 | 13.1 | 0.59 |
| Dako 22C3 (n = 534) | |||||
| 22C3 BEP | 268 | 17.5 | 266 | 14.1 | 0.82 |
| ≥ 50% TPS | 134 | 20.2 | 126 | 11.0 | 0.60 |
| ≥ 1% TPS | 213 | 17.8 | 201 | 14.0 | 0.73 |
| VENTANA SP263 (n = 546) | |||||
| SP263 BEP | 271 | 17.2 | 275 | 14.9 | 0.85 |
| ≥ 50% TC | 150 | 19.5 | 143 | 16.1 | 0.71 |
| ≥ 1% TC | 212 | 17.8 | 210 | 14.0 | 0.77 |
| Foundation Medicine bTMB (n = 389) | |||||
| bTMB BEP | 196 | 13.3 | 193 | 15.3 | 0.98 |
| ≥ 10 | 92 | 11.2 | 83 | 10.3 | 0.87 |
| ≥ 16 | 42 | 13.9 | 45 | 8.5 | 0.75 |
| ≥ 20 | 27 | 17.2 | 29 | 10.5 | 0.77 |
| a Stratified OS HRs for SP142 only. | |||||
NCT02409342
Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions, and
funded by F. Hoffmann-La Roche, Ltd