Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
completion around

Description

Summary

This Phase 1/2, open-label, multicenter study is conducted in patients with previously treated selected solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), high-grade neuroendocrine cancer of any primary site, diffuse large B-cell lymphoma (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, maximum tolerated 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 expression or amplification of L-MYC and N-MYC genes.

Official Title

A Phase 1/2 Study of Oral MRT-2359 in Patients With MYC-Driven and Other Selected Solid Tumors Including Lung Cancer and Diffuse B-Cell Lymphoma

Details

This Phase 1/2, open-label, multicenter, dose escalation and expansion study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary clinical activity of MRT-2359 in patients with previously treated selected solid tumors, including lung 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.

Keywords

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, Small Cell Lung Cancer, Non-Small Cell Lung Cancer, L-MYC Amplification, N-MYC Amplification, L-MYC expression, N-MYC expression, High-grade neuroendocrine, Diffuse Large B-Cell Lymphoma, Molecular glue degrader, Anti-tumor, GSPT1, Neuroendocrine Carcinoma, Oral MRT-2359

Eligibility

For people ages 18 years and up

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 amplification
  • NSCLC with high or low L-MYC or N-MYC expression status (testing will be provided) or SCLC

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

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. In patients with prostate cancer, continuance of systemic therapies to maintain castration levels of testosterone is allowed. Pre-menopausal patients with hormone-dependent breast cancer can continue on therapies used for suppression of ovarian function.
  • 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

Locations

  • University of California San Diego not yet accepting patients
    San Diego California 92037 United States
  • Honor Health Research Institute accepting new patients
    Scottsdale Arizona 85258 United States
  • Fred Hutchinson Cancer Center accepting new patients
    Seattle Washington 98109 United States

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
Monte Rosa Therapeutics, Inc
ID
NCT05546268
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 135 study participants
Last Updated