Among patients (pts) with advanced carcinoid/neuroendocrine tumors (NETs), expression of PD-L1 is associated with higher tumor grade. The multicohort phase 1b KEYNOTE-028 study (NCT02054806) evaluated safety and efficacy of pembrolizumab in pts with PD-L1–positive advanced solid tumors. This is the first report from the carcinoid and pancreatic NET (pNET) cohorts of this study.
Eligibility criteria included: Carcinoid tumors or well- or moderately differentiated pNETs; PD-L1–positive (≥1% modified proportion score or interface pattern, QualTek IHC); failure of standard therapy; and ECOG PS ≤ 1. Pts received pembrolizumab 10 mg/kg Q2W for up to 2 y or until confirmed progression, intolerable toxicity, or consent withdrawal. Response was assessed every 8 wk for 6 mo then every 12 wk. The primary endpoint was ORR per RECIST v1.1 by investigator review.
276 screened pts had tumor samples evaluable for PD-L1; 36% were positive. Among enrolled carcinoid (n = 25 [lung, n = 9; gut, n = 7; other, n = 9]) and pNET (n = 16) pts, respectively, median ages were 63 y and 61 y, 76% and 38% had ECOG PS of 1, and 44% and 50% had ≥2 prior therapies for metastatic disease. As of Jan 10, 2017, median (range) follow up was 18.9 (2.0–33.3) and 20.1 (4.5–30.4) mo. Treatment-related AEs (TRAEs) occurred in 17 (68%) carcinoid and 11 (69%) pNET pts; the most frequent (≥20%) were diarrhea (n = 7, 28%) and fatigue (n = 5, 20%) in carcinoid pts and fatigue (n = 6, 38%) and diarrhea (n = 4, 25%) in pNET pts. Grade ≥3 TRAEs occurred in 8 (32%) carcinoid pts (including diarrhea, n = 3; AST increased, n = 2; ALT increased; n = 2) and 0 pNET pts. One grade 4 AE (increased gamma-glutamyl transferase) and 1 death (unspecified cause) occurred in the carcinoid cohort; neither was treatment related. Three carcinoid pts (12%; 95% CI, 3%–31%) and 1 pNET pt (6%; 95% CI, 0%–30%) had objective responses; SD rates were 60% (n = 15) and 88% (n = 14). Durations of response were 6.9, 9.2, and 11.1 mo for the carcinoid responders; the pNET responder has an ongoing response of 17.6 mo.
In pts with heavily pretreated carcinoid/pNET tumors, pembrolizumab was generally well tolerated and, in some pts, provided clinically meaningful antitumor activity.
Clinical trial identification
ClinicalTrials.gov, NCT02054806; EudraCT Number, 2013-004507-39
Legal entity responsible for the study
Merck & Co., Inc., Kenilworth, NJ, USA
This research was supported by Merck & Co., Inc., Kenilworth, NJ, USA
H.S. Rugo: Research funding: Genentech/Roche, Novartis, Lilly, Eisai, Merck, Pfizer, OBI, Macrogenics, GTx pharma, Travel expenses, including accommodations: Mylan, Puma, B.H. O\'Neil: Travel expenses, including accommodations: Amgen, A. Santoro: Advisory board member: Celgene, BMS, Takeda, vierBMS, MSD, Servier, Arqule, R.B. Cohen: Advisory Board member: Takeda, BMS, Zymeworks. Research funding: Merch, Cleave, Innate. Honoraria: Takeda, BMS, Zymeworks Travel expenses, including accommodations: Takeda, BMS, Zymeworks. T. Doi: Advisory Board, Research funding: Lilly, Chugai Pharma, Kyowa Hakko Kirin, Novartis, MSD, Daiichi Sankyo. Advisory Board: Amgen. Research funding: Taiho, Merk Serono, Astellas Pharma, Janssen, Boehringer-Ingelheim, Takeda, Pfizer, Sumitomo Group, Bayer, Celgene. P.A. Ott: Research funding: BMS, Merck, Neon Therapeutics, Armo BiosSciences, Celldex, MedImmune/AZ, Pfizer, CytomX. Honoraria: BMS, Merck, Neon Therapeutics, Celldex, Prizer, CytomX, Novartis, Alexion, Genentech/Roche. C. Le Tourneau: Advisory board member: MSD, BMS, AstraZeneca, Novartis. Honoraria: Merck Serono. Travel expenses, including accommodations: MSD, AstraZeneca, BMS. J-C. Soria: Honoraria: MSD. K. Tamura: Direct research support to the responsible project lead (e.g., Principal Investigator): Daiichi Sankyo, MSD, Pfizer, AstraZeneca. M. Gould, G. Zhao: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. K. Stein: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Stock ownership: Merck, Novartis, Sanofi, Pfizer. Travel expenses, including accommodations: Merck. All other authors have declared no conflicts of interest.