RECRUITING

Study of Oral MRT-2359 in Selected Cancer Patients

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2022-10-12

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05546268

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Monte Rosa Therapeutics

CONTACT

617-865-4792

Clinicaltrials@monterosatx.com

Study Locations (Sites)

Honor Health Research Institute

Scottsdale, Arizona, 85258

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663

United States

University of California San Diego

San Diego, California, 92037

United States

Yale University

New Haven, Connecticut, 06520

United States

Sarah Cannon Research Institute

Lake Mary, Florida, 32746

United States

Indiana University

Bloomington, Indiana, 46202

United States

University of Kansas Cancer Center

Lawrence, Kansas, 66044

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Henry Ford Cancer Institute

Detroit, Michigan, 48202

United States

Washington University

Saint Louis, Missouri, 63110

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

United States

Columbia University Irving Medical Centre

New York, New York, 10032

United States

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

United States

Mary Crowley Cancer Research

Dallas, Texas, 75251

United States

MD Anderson Cancer Center

Houston, Texas, 77030-4009

United States

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229

United States

Virginia Cancer Specialists Research Institute

Fairfax, Virginia, 22031

United States

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Monte Rosa Therapeutics, Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-10-12

Study Completion Date2027-11

Study Record Updates

Study Start Date2022-10-12

Study Completion Date2027-11

Terms related to this study

Keywords Provided by Researchers

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
HR-positive
HER2-negative
Breast Cancer
Prostate Cancer

Additional Relevant MeSH Terms

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 of Oral MRT-2359 in Selected Cancer Patients

Conditions

Quick Navigation

Study Overview

Description

Official Title

Quick Facts

Study ID

Participation Criteria

Contacts and Locations

Study Contact

Study Locations (Sites)

Collaborators and Investigators

Study Record Dates

Study Registration Dates

Study Record Updates

Terms related to this study

Keywords Provided by Researchers

Additional Relevant MeSH Terms