The multicentre, open-label, Phase 3 JAVELIN Lung 200 study recruited 792 adult patients with stage IIIB/IV or recurrent NSCLC who had progressed on prior platinum-doublet chemotherapy. All participants had a performance status of 0 or 1, adequate haematological and organ function, and an estimated life expectancy of ≥12 weeks. Patients received either avelumab (10 mg/kg every two weeks) or docetaxel (75 mg/m2 every three weeks).

The protocol stipulated stratification for histology (squamous vs non-squamous) and PD-L1 expression (≥1% vs <1% of tumour cells) measured with the 73-10 assay (Dako PD-L1 IHC 73-10 pharmDx). The primary efficacy endpoint was OS and was first measured in the PD-L1 positive (≥1%) population (primary analysis population), followed by an analysis in all participants.

In total 529 patients had PD-L1 positive tumours, 264 patients of the total 396 in the avelumab group and 265 of 396 in the docetaxel group. At a median follow-up of 18.0 months and 17.8 months in the avelumab and docetaxel arms, respectively, the median OS in patients with PD-L1-positive tumours was 11.4 months (95% CI, 9.4-13.9) in the avelumab group vs 10.3 months (95% CI, 8.5-13.0) in the docetaxel group (HR=0.90; 96% CI, 0.72-1.12; one-sided p=0.1627).

The study included pre-planned exploratory analyses. A higher PD-L1 cutoff was associated with an increased OS in patients receiving avelumab vs docetaxel. Twenty-nine per cent of patients had a PD-L1-high (≥80%) expression, and the OS in this subgroup measured 17.1 months with avelumab vs 9.3 months on docetaxel (HR=0.59; 95% CI, 0.42-0.83; p=.0022, 2-sided). Among the 40% of patients with a PD-L1-medium/high (≥50%) the OS was 13.6 vs 9.2 months for avelumab vs docetaxel, respectively (HR=0.67; 95% CI, 0.51-0.89; p=0.0052, 2-sided).

The overall response rate in the PD-L1+ (≥1%) population was 18.9% with avelumab vs 11.7% with docetaxel (OR=1.76; 95% CI, 1.08-2.86; p=0.0105, 1-sided). The median duration of response was not yet reached in the avelumab-group (95% CI, 9.9-NE) vs 6.9 months in the docetaxel-group (95% CI, 3.5-NE).

In the avelumab-arm 39.8% of patients received subsequent anti-cancer treatment vs 47.5% in the docetaxel-arm, including immune-checkpoint inhibitors in 5.7% vs 26.4%, respectively. At the time of data cut-off (November 22, 2017), 15.5% vs 1.5% remained on treatment.

Safety

The safety population encompassed all patients who had received at least one dose of the study treatment. Treatment-related adverse events (TRAEs) occurred in 251 (64%) of 393 patients in the avelumab-group. In the docetaxel-group (n=365), TRAEs occurred in 313 (86%) of patients. Immune-related AEs (irAEs) of any grade occurred in 16.5% of patients receiving avelumab. Grade ≥3 irAEs were reported in 2.8% of patients on the PD-L1 inhibitor.

Grade 3-5 events were found in 39 (10%) and 180 (49%) of patients on avelumab and docetaxel, respectively. Common Grade 3-5 TRAEs in the avelumab-group included infusion-related reaction (n=6; 2%) and increased lipase (n=4; 1%). Common Grade 3-5 TRAEs in patients treated with docetaxel were neutropenia (51; 14%), febrile neutropenia (37; 10%), and decreased neutrophil counts (36; 10%). Serious TRAEs in the avelumab-group were reported in 34 (9%) of patients, compared to 75 (21%) in the docetaxel-group.

Four patients (1%) in the avelumab arm experienced a Grade 5 TRAE, including two patients with interstitial lung disease, one with an acute kidney injury, and one patient had a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure. In the docetaxel arm, Grade 5 TRAEs were reported in 14 (4%) of patients, including three (1%) pneumonia, one with febrile neutropenia, one with septic shock, one with febrile neutropenia and septic shock, one with acute respiratory failure, one with cardiovascular insufficiency, one with renal impairment, one with leucopenia plus mucosal inflammation and pyrexia, one with an infection, one with neutropenic infection, one with dehydration, and one with unknown causes.