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Poster display session

1721 - Phase 2a study of a novel stapled peptide ALRN-6924 disrupting MDMX- and MDM2-mediated inhibition of wild-type TP53 in patients with Peripheral T-Cell Lymphoma

Date

09 Sep 2017

Session

Poster display session

Topics

Lymphomas

Presenters

Marie Payton

Citation

Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373

Authors

M. Payton1, D. Pinchasik1, A. Mehta2, S. Goel3, J.M. Zain4, L. Sokol5, E. Jacobsen6, M.R. Patel7, S.M. Horwitz8, F. Meric-Bernstam9, A. Shustov10, D. Weinstock11, M. Aivado1, D.A. Annis1

Author affiliations

  • 1 Clinical Development, Aileron Therapeutics, 02139 - Cambridge/US
  • 2 Hematology & Oncology, University of Alabama at Birmingham, 35294 - Birmingham/US
  • 3 Department Of Medicine, Montefiore Medical Center, 10461 - Bronx/US
  • 4 Department Of Hematology & Hematopoietic Cell Transplantation, City of Hope, 91010 - Duarte/US
  • 5 Dept Of Hematological Malignancies, Moffitt Cancer Center, 33612 - Tampa/US
  • 6 Hematologic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 7 Oncology, Sarah Cannon Research Institute (Nashville, TN); Florida Cancer Specialists & Research Institute, 34326 - Sarasota/US
  • 8 Department Of Medicine, Memorial Sloan-Kettering Cancer Center, 10022 - New York/US
  • 9 Oncology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 10 Division Of Hematology, Seattle Cancer Care Alliance, 98109 - Seattle/US
  • 11 Weinstock Laboratory, Dana-Farber Cancer Institute, 02215 - Boston/US
More

Resources

Abstract 1721

Background

Peripheral T-cell lymphoma (PTCL) refers to a heterogeneous group of tumors that comprise a subset of T-cell non-Hodgkin lymphomas. PTCL-not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma are among the most common of these rare tumors. Outcomes are often poor, particularly in the setting of relapsed or refractory disease, making PTCL an ideal candidate for the assessment of a novel agent with strong biologic rationale. ALRN-6924 is a cell-penetrating stapled alpha-helical peptide designed to equipotently disrupt the interaction between the p53 tumor suppressor protein and its endogenous inhibitors, murine double minute X (MDMX) and 2 (MDM2). For TP53 wild-type (WT) tumors, pharmacological disruption of this interaction offers a means to induce p53-dependent cell cycle arrest and apoptosis, resulting in antitumor efficacy via a novel mechanism. ALRN-6924 demonstrated intriguing antitumor activity in a first-in-human phase 1 trial across a variety of tumor types (Meric-Bernstam et al., ASCO 2017, abstract #2505).

Trial design

This open-label Phase 2a study (NCT02264613) will enroll up to 20 adults with relapsed or refractory PTCL, after at least one prior systemic anticancer chemotherapy. Enrolled patients must have TP53 WT T-cell lymphoma (as confirmed by a central NGS testing), ECOG status of 0 or 1, and adequate organ function. Patients will receive 3.1 mg/kg ALRN-6924 as a one-hour infusion on days 1, 8, and 15 of 28-day cycles. Treatment will continue until disease progression or unacceptable toxicity. Response will be assessed according to the revised 2014 International Working Group (IWG) criteria for Lymphoma (Lugano Classification), (Cheson et al., J Clin Oncol. 2014:32:3059-3067). Primary objectives are to assess overall response rate and to further evaluate the safety and tolerability of ALRN-6924. Secondary objectives include assessment of time to response, duration of response, progression free survival, and overall survival. Pharmacodynamic biomarkers will be measured in blood and tumor samples. Recruitment is ongoing.

Clinical trial identification

NCT02264613

Legal entity responsible for the study

Aileron Therapeutics, Inc.

Funding

Aileron Therapeutics, Inc.

Disclosure

M. Payton: Employee of Aileron Therapeutics, including stock ownership. D. Pinchasik: Employee of Aileron Therapeutics, with equity. Stock ownership in Amgen. A. Mehta: Speaker bureau: Gilead Research Funding to Institution: Epizyme, Incyte, Genentech, Seattle Genetics, Bristol-Myers Squib, Merck. S. Goel: Patent “Method Of Determining The Sensitivity Of Cancer Cells To EGFR Inhibitors Including Cetuximab, Panitumumab And Erlotinib.”, Patent No. 20090258364; Honoraria: Genentech/Roche; Research Funding: Oncolytics. J.M. Zain: Speaker\'s Bureau: Malickrodt, Spectrum, Seattle Genetics Advisory Boards: Celgene, Malickrodt, Spectrum, Seattle Genetics. M.R. Patel: Honoraria and Speaker\'s Bureau: Medivation, Bristol-Myers Squib, Exelixis, Genentech, Gilead Sciences. Consulting/Advisory Board: Guardant Health. S.M. Horwitz: Consulting/Research Funding: Celgene, Takeda, Kyowa-Hakka-Kirin, Seattle Genetics, Forty-Seven, Infinity Consulting: Huya Research: ADCT, Aileron, Spectrum. F. Meric-Bernstam: Honoraria: Genentech, Roche; Consult: Genentech, Novartis, Roche, Inflection, Celgene, Pieris, Clearlight; Funding: Novartis, AstraZeneca, Taiho, Genentech, Calithera, Debiopharm, Bayer, Aileron, Puma, Verastem, CytomX, Jounce, Zymeworks, Effective, Curis. D. Weinstock: Research Funding: Aileron Therapeutics. M. Aivado, D.A. Annis: Employee of Aileron Therapeutics, with equity. All other authors have declared no conflicts of interest.

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