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A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma

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Summary

Background RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer cells over-expressing uridine cytidine kinase 2 (UCK2). Single agent RX-3117 demonstrated efficacy in a phase I trial in patients with metastatic (met) pancreatic adenocarcinoma (PC). RX-3117 plus nab-paclitaxel (nab-Pac) was evaluated as a first line treatment in met-PC cancer. Methods This was a multicenter open label phase I/II 2-stage study investigating the combination of RX3117 plus nab-Pac in the frontline treatment of patients with met-PC. The phase I portion comprised a dose de-escalation design with primary objectives of determining the safety, tolerability and recommended phase 2 dose (RP2D) of RX-3117 (orally 700, 600, or 500 mg/day for 5 consecutive days with 2 days off/week) plus nab-Pac (intravenous (IV) 125 mg/m2 once weekly) for 3 weeks with 1 week off per a 4-week cycle. The primary objective was to determine the antitumor efficacy. Results 46 patients were enrolled (22 male/24 female; median age 67; 91% Caucasian). The RP2D of RX-3117 plus nab-Pac was 700 mg/day. No dose-limiting toxicities were observed (DLTs). The overall response rate (ORR) was 23.1% and disease control rate (DCR) 74.4%. RX-3117 pharmacokinetics (PK) results were similar to previously reported monotherapy phase 1 trial. All patients experienced a treatment emergent adverse event (TEAE) with the most common diarrhea, nausea, and fatigue.10.9% of patients experienced a serious adverse event (SAE) related to the combination. Conclusion RX-3117 plus nab-Pac in newly diagnosed met-PC patients demonstrated tolerability, safety, and early treatment efficacy.

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Funding

The trial was funded by Rexahn Pharmaceuticals, currently Ocuphire Pharma.

Author information

Authors and Affiliations

  1. Formerly Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Currently Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA

    Hani Babiker

  2. Cancer Care Northwest PS, Spokane, WA, USA

    Peter J. Schlegel

  3. Baptist Lexington Associates, Lexington, KY, USA

    Lee G. Hicks

  4. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Andrea J. Bullock

  5. Joliet Oncology Hematology Associates, Joliet, IL, USA

    Nafisa Burhani

  6. Division of Hematology and Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health, San Antonio, TX, USA

    Daruka Mahadevan

  7. Division of Hematology and Oncology, Department of Medicine, University of California Irvine, Irvine, CA, USA

    Emad Elquza

  8. Division of Hematology and Oncology, Department of Medicie, Mayo Clinic, Phoenix, AZ, USA

    Mitesh J. Borad

  9. Formerly Rexahn Pharmaceuticals, Rockville, MD, USA

    Ely Benaim, Christine Peterson & Callie Heaton

  10. Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Allyson J. Ocean

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  1. Hani Babiker
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  10. Christine Peterson
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Contributions

HB is responsible for analysis, interepretation, draft and review of the manuscript, and patient recuritement. EB, CP, and CH are responsible for study design and interpretation. Remaining authors contributed to patient recruitement and review of the manuscript.

Corresponding author

Correspondence to Hani Babiker.

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Ethics approval

Not applicable.

Consent to participate

The study protocol was approved by the institutional review board at each study site. All patients signed an IRB-approved, protocol-specific written informed consent document in accordance with federal and institutional guidelines. Other disclosures: Dr Hani M Babiker is currently employed by Mayo Clinic.

Consent for publications

All authors and sponsor approved manuscript publication.

Conflicts of interest

EB, CP, and CH were employed by Rexahn pharamaceticals. Other investigators report no conflicts related to the study.

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Babiker, H., Schlegel, P.J., Hicks, L.G. et al. A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma. Invest New Drugs 40, 81–90 (2022). https://doi.org/10.1007/s10637-021-01164-9

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  • DOI: https://doi.org/10.1007/s10637-021-01164-9

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