TY - JOUR
T1 - Phase Ib Study of Ulixertinib Plus Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Adenocarcinoma
AU - Grierson, Patrick M.
AU - Tan, Benjamin
AU - Pedersen, Katrina S.
AU - Park, Haeseong
AU - Suresh, Rama
AU - Amin, Manik A.
AU - Trikalinos, Nikolaos A.
AU - Knoerzer, Deborah
AU - Kreider, Brent
AU - Reddy, Anupama
AU - Liu, Jingxia
AU - Der, Channing J.
AU - Wang-Gillam, Andrea
AU - Lim, Kian Huat
N1 - Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.
PY - 2023/2/8
Y1 - 2023/2/8
N2 - BACKGROUND: Ulixertinib is a novel oral ERK inhibitor that has shown promising single-agent activity in a phase I clinical trial that included patients with RAS-mutant cancers. METHODS: We conducted a phase Ib trial combining ulixertinib with gemcitabine and nab-paclitaxel (GnP) for untreated metastatic pancreatic adenocarcinoma. The trial comprised a dose de-escalation part and a cohort expansion part at the recommended phase II dose (RP2D). Primary endpoint was to determine the RP2D of ulixertinib plus GnP and secondary endpoints were to assess toxicity and safety profile, biochemical and radiographic response, progression-free survival (PFS) and overall survival (OS). RESULTS: Eighteen patients were enrolled. Ulixertinib 600 mg PO twice daily (BID) with GnP was initially administered but was de-escalated to 450 mg BID as RP2D early during dose expansion due to poor tolerability, which ultimately led to premature termination of the study. Common treatment-related adverse events (TRAEs) were anemia, thrombocytopenia, rash and diarrhea. For 5 response evaluable patients, one patient achieved a partial response and 2 patients achieved stable disease. For 15 patients who received the triplet, median PFS and OS were 5.46 and 12.23 months, respectively. CONCLUSION: Ulixertinib plus GnP had similar frequency of grade ≥3 TRAEs and potentially efficacy as GnP, however was complicated by a high rate of all-grade TRAEs (ClinicalTrials.gov Identifier: NCT02608229).
AB - BACKGROUND: Ulixertinib is a novel oral ERK inhibitor that has shown promising single-agent activity in a phase I clinical trial that included patients with RAS-mutant cancers. METHODS: We conducted a phase Ib trial combining ulixertinib with gemcitabine and nab-paclitaxel (GnP) for untreated metastatic pancreatic adenocarcinoma. The trial comprised a dose de-escalation part and a cohort expansion part at the recommended phase II dose (RP2D). Primary endpoint was to determine the RP2D of ulixertinib plus GnP and secondary endpoints were to assess toxicity and safety profile, biochemical and radiographic response, progression-free survival (PFS) and overall survival (OS). RESULTS: Eighteen patients were enrolled. Ulixertinib 600 mg PO twice daily (BID) with GnP was initially administered but was de-escalated to 450 mg BID as RP2D early during dose expansion due to poor tolerability, which ultimately led to premature termination of the study. Common treatment-related adverse events (TRAEs) were anemia, thrombocytopenia, rash and diarrhea. For 5 response evaluable patients, one patient achieved a partial response and 2 patients achieved stable disease. For 15 patients who received the triplet, median PFS and OS were 5.46 and 12.23 months, respectively. CONCLUSION: Ulixertinib plus GnP had similar frequency of grade ≥3 TRAEs and potentially efficacy as GnP, however was complicated by a high rate of all-grade TRAEs (ClinicalTrials.gov Identifier: NCT02608229).
KW - ERK
KW - gemcitabine
KW - pancreatic cancer
KW - ulixertinib
UR - http://www.scopus.com/inward/record.url?scp=85147783500&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyac237
DO - 10.1093/oncolo/oyac237
M3 - Article
C2 - 36427020
AN - SCOPUS:85147783500
SN - 1083-7159
VL - 28
SP - e115-e123
JO - Oncologist
JF - Oncologist
IS - 2
ER -