Oral MRT-2359 treatment for selected cancer patients

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

This study is testing a new treatment called MRT-2359 to see if it can help people with certain types of cancer that haven’t responded to other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 174 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Monte Rosa Therapeutics, Inc (industry)
• Drugs / interventions: denosumab, chemotherapy, radiation, prednisone
• Locations: 20 sites (Scottsdale, Arizona and 19 other locations)
• Trial ID: NCT05546268 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, open-label, multicenter study evaluates the safety and effectiveness of MRT-2359, a GSPT1 molecular glue degrader, in patients with previously treated solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), high-grade neuroendocrine cancer, and diffuse large B-cell lymphoma (DLBCL). The study involves a dose escalation phase to determine the maximum tolerated dose (MTD) and a subsequent phase to assess the preliminary anti-tumor activity of MRT-2359. Patients will be stratified based on specific molecular biomarkers, including L-MYC and N-MYC expression or amplification.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced solid tumors or DLBCL that have no further standard therapeutic options available.

Not a fit: Patients with early-stage cancers or those who have not been previously treated may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced cancers that have limited treatment options.

How similar studies have performed: Other studies have shown promise with molecular glue degraders, but this specific approach with MRT-2359 is novel.

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

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

Where this trial is running

Scottsdale, Arizona and 19 other locations

• Honor Health Research Institute — Scottsdale, Arizona, United States (RECRUITING)
• Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States (RECRUITING)
• University of California San Diego — San Diego, California, United States (RECRUITING)
• Yale University — New Haven, Connecticut, United States (RECRUITING)
• Sarah Cannon Research Institute — Lake Mary, Florida, United States (RECRUITING)
• Indiana University — Bloomington, Indiana, United States (TERMINATED)
• University of Kansas Cancer Center — Lawrence, Kansas, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Henry Ford Cancer Institute — Detroit, Michigan, United States (RECRUITING)
• Washington University — Saint Louis, Missouri, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (RECRUITING)
• Columbia University Irving Medical Centre — New York, New York, United States (RECRUITING)
• Sarah Cannon Research Institute — Nashville, Tennessee, United States (RECRUITING)
• Mary Crowley Cancer Research — Dallas, Texas, United States (RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) — San Antonio, Texas, United States (RECRUITING)
• Virginia Cancer Specialists Research Institute — Fairfax, Virginia, United States (RECRUITING)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (RECRUITING)
• Cross Cancer Institute — Edmonton, Alberta, Canada (RECRUITING)
• Princess Margaret Hospital — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: Monte Rosa Therapeutics

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, HR-positive, HER2-negative Breast Cancer, Prostate Cancer