2017 ASCO Annual Meeting!
Session: What's Next in Immunotherapy for Head and Neck Cancer?
Type: Clinical Science Symposium
Time: Tuesday June 6, 8:00 AM to 9:30 AM
Epacadostat plus pembrolizumab in patients with SCCHN: Preliminary phase I/II results from ECHO-202/KEYNOTE-037.
Head and Neck Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 6010)
Author(s): Omid Hamid, Todd Michael Bauer, Alexander I. Spira, Anthony J. Olszanski, Sandip Pravin Patel, Jeffrey S. Wasser, David C. Smith, Ani Sarkis Balmanoukian, Charu Aggarwal, Emmett V. Schmidt, Yufan Zhao, Hema Gowda, Tara C. Gangadhar; The Angeles Clinic and Research Institute, Los Angeles, CA; Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN; Virginia Cancer Specialists Research Institute, Fairfax, VA; Fox Chase Cancer Center, Philadelphia, PA; University of California San Diego Moores Cancer Center, La Jolla, CA; University of Connecticut Health Center, Farmington, CT; University of Michigan, Ann Arbor, MI; Abramson Cancer Center, Philadelphia, PA; Merck & Co., Inc., Kenilworth, NJ; Incyte Corporation, Wilmington, DE
Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. IDO1 overexpression has been associated with poor survival in SCCHN. Epacadostat (E) is a potent, selective oral IDO1 inhibitor. ECHO-202/KEYNOTE-037 is an open-label, phase I/II (P1/2) study evaluating E plus PD-1 inhibitor pembrolizumab (P) in multiple tumor types. We report preliminary P1/2 efficacy, safety, and tolerability findings in the SCCHN cohort as of a 29OCT2016 data cutoff. Methods: Eligible adult patients (pts) had metastatic SCCHN and received ≥1 prior chemotherapy regimen that included a platinum agent. Prior checkpoint inhibitor therapy (tx) was not permitted, and pts with carcinoma of the nasopharynx or salivary gland were excluded. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Results: A total of38 pts (P1, n = 2; P2, n = 36) were evaluated. Median age was 63 years, 87% of pts were men, 95% were white, and 66% received prior cetuximab. Of 36 efficacy-evaluable pts, 81% (n = 29) received 1–2 prior lines of tx and 19% (n = 7) received ≥3 prior lines of tx. ORR (CR+PR) and DCR (CR+PR+SD) for pts with 1–2 prior tx were 34% (2 CR, 8 PR) and 62% (8 SD), respectively; for pts with ≥3 prior tx, ORR and DCR were 14% (1 PR) and 43% (2 SD). Response was observed regardless of HPV status. At data cutoff, 9/11 responses were ongoing (range, 1+ to 563+ days). PFS and biomarker analyses are ongoing. The most common TRAEs in all 38 pts were fatigue (24%), nausea (11%), and decreased weight (11%). Grade ≥3 TRAEs occurred in 11% of pts; only increased amylase and lipase (both asymptomatic) were grade ≥3 TRAEs that occurred in > 1 pt. TRAEs led to discontinuation in 1 pt (increased amylase and lipase). Conclusions: In pts with advanced SCCHN, E + P was generally well tolerated and associated with encouraging response rates, particularly in pts with 1–2 prior lines of tx. A phase III SCCHN study is planned. Clinical trial information: NCT02178722