Background: Dual blockade of EGFR and VEGFR pathways in EGFRm NSCLC augments anti-tumor efficacy versus (v) EGFR inhibition alone. RELAY (NCT02411448) evaluated efficacy and safety of ERL, an EGFR TKI standard-of-care, plus RAM, a human IgG₁ VEGFR2 antagonist, or PL in 1L EGFRm metastatic NSCLC. Methods: Eligibility included untreated metastatic NSCLC pts with Exon 19 deletion (del) or L858R and no CNS metastasis. Randomized (1:1) pts received ERL (150 mg/day) + RAM (10 mg/kg q2w) or ERL + PL, stratified by gender, geographic region (East Asia v other), EGFRm type (Ex19del v L858R) and EGFR testing method (Therascreen/Cobas v other). The primary endpoint was Investigator assessed progression free survival (PFS). Other objectives included ORR, DoR, PFS2, OS, safety, and plasma T790M mutation (Guardant NGS). Results: 449 pts were randomized characteristics were balanced between treatment arms: Asian 77%, Females 63%, Ex19del 54%. RAM + ERL significantly prolonged PFS, DoR, and PFS2 (Table). Grade >=3 TEAEs were greater with RAM (72%) v PL (54%), largely driven by hypertension (24 v 5%, no Gr4); with 1 treatment related on study death (hemothorax) in RAM v 0 PL. EGFR T790M+ rates at progression are forthcoming. Conclusion: RAM + ERL led to superior PFS in 1L EGFRm metastatic NSCLC. Safety was consistent with the established safety profiles of the individual compounds. Clinical trial information: NCT02411448

Median follow-up: 20.7 months NR, not reached * unstratified **Ns are based on number of responders from the ITT population