ECHO-310: A phase 3, randomized trial of epacadostat + nivolumab + chemo vs EXTREME as first-line treatment of recurrent/metastatic SCCHN.

TPS6092 Background: Novel combination treatments targeting broad immunosuppression in the tumor microenvironment (TME) may improve patient (pt) survival. Nivolumab (N) is a PD-1 inhibitor that was shown to significantly prolong overall survival (OS) in pts with platinum-refractory r/m SCCHN. Epacadostat (E) is a potent, highly selective oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that contributes to immunosuppression in the TME. Preliminary phase 2 findings from the ECHO-204 study suggest encouraging efficacy with E + N in pts with r/m SCCHN. The ECHO-310 study (NCT03342352) compares E + N + chemo vs the EXTREME regimen as first-line treatment for r/m SCCHN. Methods: Eligible pts are ≥18 years old with treatment-naive r/m SCCHN (oral cavity, oropharynx, hypopharynx, and larynx), ECOG PS ≤1, and no prior IDO inhibitors or immune checkpoint therapies. Approximately 550 pts will be randomized (2:2:1) into 3 arms: Arm A receives blinded E 100 mg BID + N 360 mg Q3W + 6 cycles of chemo (cisplatin 100 mg/m2 in Cycle 1, then 75 mg/m2 Q3W in Cycles 2–6 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2 on Days 1–4 of each cycle); Arm B (EXTREME) receives cisplatin 100 mg/m2 Q3W or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2 on Days 1–4 of each cycle + cetuximab 400 mg/m2 on Cycle 1 Day 1, then 250 mg/m2 QW (starting Cycle 1 Day 8); and Arm C receives E-matched placebo BID + N 360 mg Q3W + 6 cycles of chemo (same as Arm A). Randomization will be stratified by PD-L1 status (expressing [≥1%] vs nonexpressing [ < 1%]/nonevaluable), HPV status (oropharyngeal p16 positive vs oropharyngeal p16 negative/nonoropharyngeal SCC), and investigator’s choice of cisplatin vs carboplatin. E and placebo treatment continue for up to 2 years or until permanent discontinuation of N, disease progression, unacceptable adverse event (AE), or consent withdrawal. Primary endpoints: OS and PFS in Arms A and B. Secondary endpoints: ORR and duration of response (DOR) in Arms A and B; ORR, PFS, and DOR in Arm C; and quality of life in Arms A and B. Tumor assessments (RECIST v1.1) are performed Q6W for 48 weeks and Q12W thereafter. AEs, graded per CTCAE v4.0, are evaluated for at least 100 days after end of treatment. Clinical trial information: NCT03342352.