RELAY+: Exploratory study of ramucirumab plus gefitinib in untreated patients (pts) with epidermal growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer (NSCLC).

Abstract

9564 Background: The phase III randomized part of the RELAY study (Part B; RELAY; NCT02411448) showed a significant improvement in progression-free survival (PFS) for ramucirumab (RAM) plus erlotinib (ERL) vs placebo plus ERL in 449 untreated pts with EGFR-mutated metastatic NSCLC (median PFS: 19.4 vs 12.4 months; stratified hazard ratio: 0.59, 95% CI: 0.46–0.76, p<0.0001; 1-year PFS rate: 71.9% vs 50.7%). Here we report initial results from RELAY+ (additional cohort of RELAY; Part C), an open-label, single-arm, exploratory study evaluating RAM plus gefitinib (GEF) in East Asian pts. Methods: Previously untreated East Asian pts with metastatic NSCLC and EGFR exon 19 deletions (Ex19del) or exon 21 substitution mutation (Ex21.L858R) received RAM (10 mg/kg Q2W) plus GEF (250 mg/day) until disease progression or unacceptable toxicity. The 1-year PFS rate (primary endpoint, assuming a 1-year PFS rate of 55% for RAM+GEF), tumor response, biomarkers, and safety were assessed. EGFR T790M status (baseline/30-day follow-up) was assessed in liquid biopsy samples by Guardant360 NGS. Results: In total, 82 pts were enrolled (Japan: 68; Taiwan: 8; Korea: 6); 65.9% were female, 65.9% were never-smokers, and 43.9% had Ex19del. With median follow-up of 13.8 months (range: 2.6–20.2; censoring rate: 58.5%), the overall 1-year PFS rate (95% CI) was 65.0% (52.4–75.1), 67.2% (48.6–80.3) in pts with Ex19del (n=36), and 63.4% (45.0–77.1) in pts with Ex21.L858R (n=46). The objective response rate was 70.7% (95% CI: 59.6–80.3), disease control rate was 98.8% (95% CI: 93.4–100.0), and duration of response was immature at this point in time with a censoring rate of 56.9% where the median point estimate was 13.6 months (95% CI: 11.1–18.2). Post-progression EGFR T790M was seen in 7 of 9 (78%; 95% CI: 45.3–93.7) pts with 30-day follow-up NGS results in which EGFR activating mutation was detected. Grade ≥3 treatment-emergent adverse events reported in >5% of pts were ALT increased (23.2%), hypertension (22.0%), and AST increased (12.2%). Conclusions: With a 1-year PFS rate of 65.0%, the primary endpoint of RELAY+ was met. The efficacy of RAM+GEF in RELAY+ was similar to that of RAM+ERL in RELAY, and the safety profile of the combination was similar to that of the individual drugs. Clinical trial information: NCT02411448 .