Study of Oral MRT-2359 in Selected Cancer Patients

NCT05546268 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: MRT-2359-001
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 17

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

Conditions

NSCLC With High or Low L-MYC or N-MYC Expression; NSCLC; SCLC; High Grade Neuroendocrine Cancer; DLBCL; HR-positive, HER2-negative Breast Cancer; Prostate Cancer; L-MYC and N-MYC Amplified Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase 1 Evaluates safety and tolerability of MRT-2359 over a 28-day cycle by the occurrence and frequency of dose limiting toxicities (DLTs) for determination of the MTD and/or RP2D

  28 days

• Phase 2 Evaluates preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1

  56 days (up to approximately 24 months from screening to end of study participation

Secondary Outcomes (11)

• Phase 1 safety and tolerability of MRT-2359 (orally over a 28-day cycle) by the nature, incidence, and severity of all treatment-emergent adverse events (TEAEs), including treatment-related TEAEs and serious adverse events (SAEs)

  18 months

• Phase 1 preliminary anti-tumor activity: ORR (RECIST 1.1/Revised Response Criteria for Malignant Lymphoma),duration of response for complete response(CR)/partial response(PR), disease control rate, progression-free survival, overall survival

  18 months

• Phase 1 Dose Escalation characterizes the PK profile of MRT-2359 by standard primary PK parameters including, but not limited to, AUC, Cmax, tmax, and t1/2

  28 days

• Phase 1 Dose Escalation evaluates the effect of a high-fat meal on the relative bioavailability of MRT-2359 by standard primary PK parameters including, but not limited to, AUC and Cmax

  7 days

• Phase 2 Dose Expansion evaluates the safety and tolerability of MRT-2359 administered orally over a 28-day cycle by the nature, incidence, and severity of all TEAEs, including treatment-related TEAEs and SAEs according to the NCI CTCAE, version 5.0

  24 months

Study Arms (6)

Phase 1 Dose Escalation

EXPERIMENTAL

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

Phase 2 Expansion - NSCLC

EXPERIMENTAL

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

Drug: Oral MRT-2359

Phase 2 Expansion - SCLC

EXPERIMENTAL

Patients with SCLC

Drug: Oral MRT-2359

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

EXPERIMENTAL

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

Drug: Oral MRT-2359

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

EXPERIMENTAL

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

Drug: Oral MRT-2359

Phase 2 Expansion - Prostate Cancer

EXPERIMENTAL

Patients with prostate cancer in combination with enzalutamide

Drug: Oral MRT-2359

Interventions

Oral MRT-2359 DRUG

Orally administered tablets of MRT-2359.

Phase 1 Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Monte Rosa Therapeutics, Inc: lead

Study Sites (17)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of California San Diego

San Diego, California, 92037, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Kansas Cancer Center

Lawrence, Kansas, 66044, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49546, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Columbia University Irving Medical Centre

New York, New York, 10032, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

South Texas Accelerated Research Therapeutics (START) Mountain Region

West Valley City, Utah, 84119, United States

Location

Virginia Cancer Specialists Research Institute

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Lymphoma, Large B-Cell, Diffuse; Breast Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 19, 2022
• Study Start: October 12, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)