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Study of Oral MRT-2359 in Selected Cancer Patients

Primary Purpose

NSCLC, SCLC, High Grade Neuroendocrine Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oral MRT-2359
Oral MRT-2359
Oral MRT-2359
Oral MRT-2359
Sponsored by
Monte Rosa Therapeutics, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NSCLC focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Honor Health Research InstituteRecruiting
  • Indiana UniversityRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Columbia University Irving Medical CentreRecruiting
  • Sarah Cannon Research InstituteRecruiting
  • Mary Crowley Cancer ResearchRecruiting
  • MD Anderson Cancer CenterRecruiting
  • South Texas Accelerated Research Therapeutics (START)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1 Dose Escalation

Phase 2 Expansion - NSCLC

Phase 2 Expansion - SCLC

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

Arm Description

Patients with NSCLC, SCLC, high-grade neuroendocrine cancer of any primary site, any solid tumors with L-MYC or N-MYC amplification, or DLBCL

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

Patients with SCLC with high or low L-MYC or N-MYC mRNA expression

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)
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
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
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
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
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
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.

Full Information

First Posted
September 16, 2022
Last Updated
August 30, 2023
Sponsor
Monte Rosa Therapeutics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05546268
Brief Title
Study of Oral MRT-2359 in Selected Cancer Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 27, 2022 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
November 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Monte Rosa Therapeutics, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single Group
Masking
None (Open Label)
Masking Description
None (Open Label)
Allocation
Non-Randomized
Enrollment
133 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Dose Escalation
Arm Type
Experimental
Arm Description
Patients with NSCLC, SCLC, high-grade neuroendocrine cancer of any primary site, any solid tumors with L-MYC or N-MYC amplification, or DLBCL
Arm Title
Phase 2 Expansion - NSCLC
Arm Type
Experimental
Arm Description
Patients with NSCLC with high or low L-MYC or N-MYC mRNA expression
Arm Title
Phase 2 Expansion - SCLC
Arm Type
Experimental
Arm Description
Patients with SCLC with high or low L-MYC or N-MYC mRNA expression
Arm Title
Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors
Arm Type
Experimental
Arm Description
Patients with L-MYC or N-MYC amplified solid tumors
Intervention Type
Drug
Intervention Name(s)
Oral MRT-2359
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Oral MRT-2359
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Oral MRT-2359
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Oral MRT-2359
Intervention Description
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)
Primary Outcome Measure Information:
Title
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
Title
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 Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Monte Rosa Therapeutics
Phone
617-865-4792
Email
Clinicaltrials@monterosatx.com
Facility Information:
Facility Name
Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Recruiting
Facility Name
Indiana University
City
Bloomington
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Irving Medical Centre
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Mary Crowley Cancer Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Individual Site Status
Recruiting
Facility Name
South Texas Accelerated Research Therapeutics (START)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Oral MRT-2359 in Selected Cancer Patients

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