Study of Oral MRT-2359 in Selected Cancer Patients

• ClinicalTrials.gov Identifier: NCT05546268
• Recruitment Status: Recruiting
• First Posted: September 19, 2022
• Last Update Posted: August 31, 2023
• Sponsor: Monte Rosa Therapeutics, Inc
• Information provided by (Responsible Party): Monte Rosa Therapeutics, Inc

Study Description

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 mRNA expression or amplification of L-MYC and N-MYC genes.

Condition or disease	Intervention/treatment	Phase
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; SCLC With High or Low L-MYC or N-MYC Expression	Drug: Oral MRT-2359	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 133 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single Group
• Masking: None (Open Label)
• Masking Description: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 27, 2022
• Estimated Primary Completion Date: May 2026
• Estimated Study Completion Date: November 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: Oral MRT-2359; Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)
Experimental: Phase 2 Expansion - NSCLC; Patients with NSCLC with high or low L-MYC or N-MYC mRNA expression	Drug: Oral MRT-2359; Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)
Experimental: Phase 2 Expansion - SCLC; Patients with SCLC with high or low L-MYC or N-MYC mRNA expression	Drug: Oral MRT-2359; Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)
Experimental: Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors; Patients with L-MYC or N-MYC amplified solid tumors	Drug: Oral MRT-2359; Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 28 days ]
2. Phase 2 Evaluates preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1 [ Time Frame: 56 days (up to approximately 24 months from screening to end of study participation ]

Secondary Outcome Measures :

1. 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) [ Time Frame: 18 months ]
2. 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 [ Time Frame: 18 months ]
3. 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 [ Time Frame: 28 days ]
4. 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 [ Time Frame: 7 days ]
5. 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 [ Time Frame: 24 months ]
6. Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DoR (in patients with the best overall response of CR or PR), DCR, PFS, and OS [ Time Frame: 24 months ]
7. Phase 2 Dose Expansion further characterizes the PK profile of MRT-2359 by evaluating MRT-2359 plasma concentration to establish PK parameters including, but not limited to, Cmax, tmax, AUC0-t, AUC0-inf, mean residence time, accumulation ratio, etc. [ Time Frame: 28 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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
• 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

Contacts

Contact: Monte Rosa Therapeutics; 617-865-4792; Clinicaltrials@monterosatx.com

Locations

United States, Arizona

Honor Health Research Institute; Recruiting

Scottsdale, Arizona, United States, 85258

United States, Indiana

Indiana University; Recruiting

Bloomington, Indiana, United States, 46202

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10021

Columbia University Irving Medical Centre; Recruiting

New York, New York, United States, 10032

United States, Tennessee

Sarah Cannon Research Institute; Recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

Mary Crowley Cancer Research; Recruiting

Dallas, Texas, United States, 75251

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030-4009

South Texas Accelerated Research Therapeutics (START); Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Monte Rosa Therapeutics, Inc

More Information

• Responsible Party: Monte Rosa Therapeutics, Inc
• ClinicalTrials.gov Identifier: NCT05546268
• Other Study ID Numbers: MRT-2359-001
• First Posted: September 19, 2022
• Last Update Posted: August 31, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Monte Rosa Therapeutics, Inc:

High-grade neuroendocrine; Small Cell Lung Cancer; Non-Small Cell Lung Cancer; L-MYC Amplification; N-MYC Amplification; L-MYC expression; N-MYC expression; Diffuse Large B-Cell Lymphoma; Molecular glue degrader; Anti-tumor; GSPT1

Additional relevant MeSH terms:

Carcinoma, Neuroendocrine; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue