PMID- 38530565
OWN - NLM
STAT- Publisher
LR  - 20240326
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
DP  - 2024 Mar 26
TI  - KEYNOTE-434 part B: A phase 1 study evaluating the combination of epacadostat, 
      pembrolizumab, and chemotherapy in Japanese patients with previously untreated 
      advanced non-small-cell lung cancer.
LID - 10.1007/s10637-024-01422-6 [doi]
AB  - BACKGROUND: Pembrolizumab plus epacadostat (indoleamine 2,3-dioxygenase-1 
      inhibitor) was well tolerated in Japanese patients with advanced solid tumors in 
      part A of the nonrandomized, open-label, phase 1 KEYNOTE-434 study (NCT02862457). 
      We report results from part B, which evaluated epacadostat plus pembrolizumab and 
      chemotherapy in Japanese patients with advanced non-small-cell lung cancer 
      (NSCLC). METHODS: Eligible patients aged >/= 20 years had histologically or 
      cytologically confirmed stage IIIB or IV NSCLC with no prior systemic therapy, 
      and ECOG performance status of 0 or 1. Patients received epacadostat 100 mg 
      orally twice-daily, pembrolizumab 200 mg intravenously every-3-weeks for </= 35 
      cycles, and 4 cycles of chemotherapy (cohort 1: cisplatin plus pemetrexed, 
      non-squamous; cohort 2: carboplatin plus pemetrexed, non-squamous; cohort 3: 
      carboplatin plus paclitaxel, squamous or non-squamous). Primary endpoint was 
      incidence of dose-limiting toxicities (DLTs). Following unfavorable results from 
      other studies, a protocol amendment removed epacadostat from the treatment 
      combination. RESULTS: Of 19 patients, 7 were enrolled in cohort 1, and 6 each in 
      cohorts 2 and 3. Median follow-up was 13.7 (range, 4.2-27.8) months. Five of 17 
      (29%) DLT-evaluable patients experienced >/= 1 DLT (cohort 1, n = 1; cohorts 2 and 
      3, n = 2 each); most commonly maculopapular rash (grade 3, n = 3) and increased 
      alanine aminotransferase (grade 2, n = 1; grade 3, n = 2). All patients 
      experienced treatment-related adverse events (AEs); 58% experienced grade 3 or 4 
      treatment-related AEs. Objective response rate was 47%. CONCLUSION: The 
      combination of epacadostat plus pembrolizumab and chemotherapy was found to be 
      tolerable in Japanese patients with advanced NSCLC. TRIAL REGISTRATION: 
      ClinicalTrials.gov , NCT02862457.
CI  - (c) 2023. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.
FAU - Yamamoto, Noboru
AU  - Yamamoto N
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, 5 
      Chome-1-1 Tsukiji, Tokyo, Japan. nbryamam@ncc.go.jp.
FAU - Satouchi, Miyako
AU  - Satouchi M
AD  - Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
FAU - Doi, Toshihiko
AU  - Doi T
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital East, 
      Kashiwa, Japan.
FAU - Fujiwara, Yutaka
AU  - Fujiwara Y
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, 5 
      Chome-1-1 Tsukiji, Tokyo, Japan.
AD  - Department of Thoracic Oncology, Aichi Cancer Center, Aichi, Japan.
FAU - Yanagitani, Noriko
AU  - Yanagitani N
AD  - Department of Thoracic Medical Oncology, The Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, Tokyo, Japan.
FAU - Kawa, Yoshitaka
AU  - Kawa Y
AD  - Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
FAU - Yoh, Kiyotaka
AU  - Yoh K
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital East, 
      Kashiwa, Japan.
FAU - Leopold, Lance
AU  - Leopold L
AD  - Incyte Corporation, Clinical Development, Wilmington, DE, USA.
FAU - Munteanu, Mihaela
AU  - Munteanu M
AD  - Incyte Corporation, Clinical Development, Wilmington, DE, USA.
FAU - Sawada, Takashi
AU  - Sawada T
AD  - MSD K.K. Oncology Science Unit, Tokyo, Japan.
FAU - Han, Shirong
AU  - Han S
AD  - MSD K.K. Oncology Science Unit, Tokyo, Japan.
FAU - Noguchi, Kazuo
AU  - Noguchi K
AD  - MSD K.K. Oncology Science Unit, Tokyo, Japan.
FAU - Nishio, Makoto
AU  - Nishio M
AD  - Department of Thoracic Medical Oncology, The Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02862457
PT  - Journal Article
DEP - 20240326
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
SB  - IM
OTO - NOTNLM
OT  - Clinical trial, phase 1
OT  - Indoleamine 2,3-dioxygenase
OT  - Non‒small-cell lung cancer
OT  - Pembrolizumab
EDAT- 2024/03/26 18:43
MHDA- 2024/03/26 18:43
CRDT- 2024/03/26 12:22
PHST- 2023/12/06 00:00 [received]
PHST- 2024/01/15 00:00 [accepted]
PHST- 2024/03/26 18:43 [medline]
PHST- 2024/03/26 18:43 [pubmed]
PHST- 2024/03/26 12:22 [entrez]
AID - 10.1007/s10637-024-01422-6 [pii]
AID - 10.1007/s10637-024-01422-6 [doi]
PST - aheadofprint
SO  - Invest New Drugs. 2024 Mar 26. doi: 10.1007/s10637-024-01422-6.