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Clinical Trial
. 2023 Feb 8;28(2):e115-e123.
doi: 10.1093/oncolo/oyac237.

Phase Ib Study of Ulixertinib Plus Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Adenocarcinoma

Patrick M Grierson  1 , Benjamin Tan  1 , Katrina S Pedersen  1 , Haeseong Park  1 , Rama Suresh  1 , Manik A Amin  2 , Nikolaos A Trikalinos  1 , Deborah Knoerzer  3 , Brent Kreider  3 , Anupama Reddy  3 , Jingxia Liu  4 , Channing J Der  5 , Andrea Wang-Gillam  1 , Kian-Huat Lim  1
Affiliations
Clinical Trial

Phase Ib Study of Ulixertinib Plus Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Adenocarcinoma

Patrick M Grierson et al. Oncologist. .

Abstract

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).

Keywords: ERK; gemcitabine; pancreatic cancer; ulixertinib.

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Figures

Figure 1.
Figure 1.
Treatment course of all 18 enrolled patients. 15 patients received ulixertinib plus GnP.
Figure 2.
Figure 2.
(A) Consort diagram showing enrollment of patients on this study. (B) CA19-9 percent change from baseline of 9 patients with available pre- and post-treatment CA19-9 values. Three other patients without elevated CA19-9 values were not included. (C) PFS and (D) OS of all 15 patients who started triplet therapy.
Figure 3.
Figure 3.
(A) IHC staining and (B) bulk RNaseq of 7 paired biopsy specimens treated with ulixertinib 600 mg BID lead-in for 2 weeks.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A.. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. 10.3322/caac.21708. - DOI - PubMed
    1. Conroy T, Desseigne F, Ychou M, et al. . Folfirinox versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. 10.1056/NEJMoa1011923. - DOI - PubMed
    1. Von Hoff DD, Ervin T, Arena FP, et al. . Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. 10.1056/NEJMoa1304369. - DOI - PMC - PubMed
    1. Biankin AV, Waddell N, Kassahn KS, et al. . Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491(7424):399-405. 10.1038/nature11547. - DOI - PMC - PubMed
    1. Waddell N, Pajic M, Patch AM, et al. . Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518(7540):495-501. 10.1038/nature14169. - DOI - PMC - PubMed

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