Study of Oral MRT-2359 in Selected Cancer Patients

M
Mateusz Opyrchal, MD, PhD

Primary Investigator

Overview

This Phase 1/2, open-label, multicenter study is conducted in patients with previouslyd selected solid tumors, including non-small cell lung cancer (NSCLC), small cell lung(SCLC), high-grade neuroendocrine cancer of any primary site, diffuse large B-cellymphoma (DLBCL), and tumors with L-MYC or N-MYC amplification. Patients receive escalating doses of a GSPT1 molecular glue degrader MRT-2359 to determine safety, tolerability, maximumd dose (MTD) and/or recommended Phase 2 dose (RP2D) of MRT-2359. Once the MTD and/or RP2D is identified, additional patients enroll to Phase 2 study, which includes molecular biomarkers stratification or selection, namely mRNA expression or amplification of L-MYC andYC genes.

Description

This Phase 1/2, open-label, multicenter, dose escalation and expansion study to assess they, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary clinicalvity of MRT-2359 in patients with previously treated selected solid tumors, includingung cancer (NSCLC and SCLC), high-grade neuroendocrine cancer of any primary site, and DLBCL.
  • The primary aim of Phase 1 part is safety, tolerability, MTD and/or RP2D of MRT-2359.
  • The primary aim of Phase 2 part is assessment of preliminary anti-tumor activity of MRT-2359.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    NSCLC, SCLC, High Grade Neuroendocrine Cancer, DLBCL, L-MYC and N-MYC Amplified Solid Tumors, NSCLC With High or Low L-MYC or N-MYC Expression, SCLC With High or Low L-MYC or N-MYC Expression
  • Age: 18 Years
  • Gender: All

Phase 1 enrollment population:
  • NSCLC
  • SCLC
  • High-grade neuroendocrine cancer of any primary site
  • Any solid tumors with L-MYC or N-MYC amplification
  • DLBCL
Phase 2 enrollment population:
  • Any solid tumors with L-MYC or N-MYC known amplification
  • NSCLC or SCLC with known L-MYC or N-MYC mRNA expression status (testing will bevided)
Phase 1 and Phase 2 Inclusion Criteria:
  • Have a selected advanced solid tumor or DLBCL (listed above) for which there are nourther standard therapeutic options available
  • Be age ≥ 18 years and willing to voluntarily complete the informed consent process
  • A predicted life expectancy of ≥ 3 months and an ECOG performance status ≤ 2
  • Have measurable disease by RECIST 1.1 (Eisenhauer et al., 2009) in case of solidumors or Revised Response Criteria for Malignant Lymphoma (Phase 1 only) (Cheson et., 2014) in case of DLBCL
  • Have adequate organ function defined by the selected laboratory parameters
  • If female of childbearing potential, avoid becoming pregnant and agree to useble methods of contraception after informed consent, throughout the study, and90 days after the last dose of MRT-2359
  • Male of reproductive potential must use an approved methods of contraception fromd consent until 90 days after study discharge
Exclusion Criteria:
  • Have received prior chemotherapy, definitive radiation, biological cancer therapy ory investigational agent within 21 days before the first dose of study treatment, orhave any AEs that have failed to recover to baseline
  • Have received bisphosphonates or denosumab within 14 days before the firstdministration of the study drug unless they were given for acute hypercalcemia
  • Inability to swallow oral medication
  • Have received prior therapy with a GSPT1 degrader that was discontinued due to an AE
  • Have received prior auto-HCT and not fully recovered from effects of the last
  • Have received prior allogeneic hematopoietic stem cell transplantation within past 6hs and/or have symptoms of graft-versus-host disease. Patients requiring minimalvention such as topical steroids are eligible
  • Have received a live vaccine within 90 days before the first dose of study treatment
  • COVID-19 immunization within 14 days of receiving the first dose of MRT-2359
  • Current use of chronic systemic steroid therapy in excess of replacement doses(prednisone ≤ 10 mg/day is acceptable)
  • Have clinically significant active malabsorption syndrome or other condition likely togastrointestinal absorption of the study drug
  • Have a history of a second malignancy, unless controlled not requiring therapy
  • Have clinically active central nervous system involvement and/or carcinomatousgitis. Patients with treated and stable brain metastases (not progressing for atweeks prior to enrollment) not requiring steroids are eligible
  • Have a confirmed history of (non-infectious) pneumonitis that required steroids
  • Have known human immunodeficiency virus (HIV) unless the patient is on antiviralherapy with undetectable HIV RNA levels
  • Have known hepatitis B or C infection(s) unless treated with undetectable hepatitis BDNA or hepatitis C RNA levels
  • Clinically significant cardiac disease
  • Be pregnant or breastfeeding

Updated on 04 May 2024. Study ID: MRT-2359-001
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