A Phase I/II Study of Oral MRT-2359 in Patients With MYC-Driven and Other Selected Solid Tumors Including Lung Cancer and Diffuse B-Cell Lymphoma

Study Identifier:
MRT-2359-001
CT.gov Identifier:
NCT05546268
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To evaluate MRT-2359 in patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and other solid tumours.

To evaluate the safety, tolerability and anti-tumor activity of MRT-2359.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Non-Small Cell Lung Cancer
  • Small Cell Lung
  • Neuroendocrine
  • Lymphoma
  • Solid Tumor
  • Biomarkers
  • Breast Cancers
  • Prostate
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Phase 1 Dose Escalation Patients with NSCLC, SCLC, high-grade neuroendocrine cancer of any primary site, any solid tumors with L-MYC or N-MYC amplification, or DLBCL Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose) Experimental: Phase 2 Expansion - NSCLC Patients with NSCLC with high or low L-MYC or N-MYC mRNA expression Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose) Experimental: Phase 2 Expansion - SCLC Patients with SCLC with high or low L-MYC or N-MYC mRNA expression Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose) Experimental: Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors Patients with L-MYC or N-MYC amplified solid tumors Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose) Patients receives MRT-2359 at 1.5 mg in a 5 days on-drug, 9 days off-drug dosing schedule and, based on the observed safety profile, is considering a 21 days on-drug, 7 days off-drug dosing regimen. Experimental: Phase 2 Expansion - HR-positive, HER2-negative breast cancer Patients with HR-positive, HER2-negative breast cancer in combination with fulvestrant Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant. Experimental: Phase 2 Expansion - Prostate Cancer Patients with prostate cancer in combination with enzalutamide Drug: Oral MRT-2359 Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide. 0.5mg dose with the 21 days on, 7 days off regimen a potential recommended Phase 2 dose. 0.75 mg, 21 days on, 7 days off dose cohort
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • 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 be provided) HR-positive, HER2-negative breast cancer - MRT-2359 in combination with fulvestrant Non-neuroendocrine prostate cancer - MRT-2359 in combination with enzalutamide Phase 1 and Phase 2 Inclusion Criteria: Have a selected advanced solid tumor or DLBCL (listed above) for which there are no further 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 solid tumors or Revised Response Criteria for Malignant Lymphoma (Phase 1 only) (Cheson et al., 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 use acceptable methods of contraception after informed consent, throughout the study, and for 90 days after the last dose of MRT-2359 Male of reproductive potential must use an approved methods of contraception from informed consent until 90 days after study discharge
    • Patients (Major eligibility criteria)
    • Non-neuroendocrine mCRPC prostate cancer patients with a focus on the following patient
    • subsets:
    • • Have received prior abiraterone but not a 2nd generation ARi
    • • Harbor mutations in AR such as L702H, AR T878A/S, AR H875Y, or similar pathogenic
    • mutations detected by ctDNA or molecular testing of tumor tissue
    • • At least one measurable lesion according to RECIST v1.1
    • • ECOG≤ 2
    Exclusion criteria
    • Have received prior chemotherapy, definitive radiation, biological cancer therapy or any investigational agent within 21 days before the first dose of study treatment, or have any AEs that have failed to recover to baseline
    • Have received bisphosphonates or denosumab within 14 days before the first administration 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 transplant
    • Have received prior allogeneic hematopoietic stem cell transplantation within past 6 months and/or have symptoms of graft-versus-host disease. Patients requiring minimal intervention 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 to affect gastrointestinal 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 carcinomatous meningitis. Patients with treated and stable brain metastases (not progressing for at least 4 weeks 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 antiviral therapy with undetectable HIV RNA levels
    • Have known hepatitis B or C infection(s) unless treated with undetectable hepatitis B DNA or hepatitis C RNA levels
    • Clinically significant cardiac disease
    • Be pregnant or breastfeeding

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Kyriakos Papadopoulos
    Status
    Recruiting
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Small Cell Lung
    Neuroendocrine
    Lymphoma
    Solid Tumor
    Biomarkers
    Breast Cancers
    Prostate
    Location
    START Mountain Region
    West Valley City, UT, United States, 84119
    Investigator
    William McKean
    Status
    Recruiting
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Small Cell Lung
    Neuroendocrine
    Lymphoma
    Solid Tumor
    Biomarkers
    Breast Cancers
    Prostate
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Sreenivasa Chandana
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Small Cell Lung
    Neuroendocrine
    Lymphoma
    Solid Tumor
    Biomarkers
    Breast Cancers
    Prostate