Study of Oral MRT-2359 in Selected Cancer Patients

NCT ID: NCT05546268

Last Updated: 2025-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-12

Study Completion Date

2027-11-30

Brief Summary

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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, hormone receptor positive (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer and prostate cancer.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Single Group
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

None (Open Label)

Study Groups

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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

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359.

Phase 2 Expansion - NSCLC

Patients with NSCLC with high or low L-MYC or N-MYC expression

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359.

Phase 2 Expansion - SCLC

Patients with SCLC

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359.

Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors

Patients with L-MYC or N-MYC amplified solid tumors

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359.

Phase 2 Expansion - HR-positive, HER2-negative breast cancer

Patients with HR-positive, HER2-negative breast cancer in combination with fulvestrant

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.

Phase 2 Expansion - Prostate Cancer

Patients with prostate cancer in combination with enzalutamide

Group Type EXPERIMENTAL

Oral MRT-2359

Intervention Type DRUG

Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.

Interventions

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Oral MRT-2359

Orally administered tablets of MRT-2359.

Intervention Type DRUG

Oral MRT-2359

Orally administered tablets of MRT-2359.

Intervention Type DRUG

Oral MRT-2359

Orally administered tablets of MRT-2359.

Intervention Type DRUG

Oral MRT-2359

Orally administered tablets of MRT-2359.

Intervention Type DRUG

Oral MRT-2359

Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.

Intervention Type DRUG

Oral MRT-2359

Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Monte Rosa Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Honor Health Research Institute

Scottsdale, Arizona, United States

Site Status RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status RECRUITING

University of California San Diego

San Diego, California, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status ACTIVE_NOT_RECRUITING

Sarah Cannon Research Institute

Lake Mary, Florida, United States

Site Status RECRUITING

Indiana University

Bloomington, Indiana, United States

Site Status WITHDRAWN

University of Kansas Cancer Center

Lawrence, Kansas, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Columbia University Irving Medical Centre

New York, New York, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START) Mountain Region

West Valley City, Utah, United States

Site Status RECRUITING

Virginia Cancer Specialists Research Institute

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status ACTIVE_NOT_RECRUITING

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Canada

Central Contacts

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Monte Rosa Therapeutics

Role: CONTACT

617-865-4792

Other Identifiers

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MRT-2359-001

Identifier Type: -

Identifier Source: org_study_id

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