Study of Oral MRT-2359 in Selected Cancer Patients

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546268
• Other study ID #: MRT-2359-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 12, 2022
• Est. completion date: November 2027

Study information

• Verified date: April 2024
• Source: Monte Rosa Therapeutics, Inc
• Contact: Monte Rosa Therapeutics
• Phone: 617-865-4792
• Email: Clinicaltrials[@]monterosatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: November 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 amplification

• NSCLC with high or low L-MYC or N-MYC expression status (testing will be provided) or SCLC

• HR-positive, HER2-negative breast cancer - MRT-2359 in combination with fulvestrant

• Non-neuroendocrine prostate cancer - MRT-2359 in combination with enzalutamide

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. 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

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• DLBCL
• NSCLC
• Prostate Cancer
• Prostatic Neoplasms
• SCLC

Intervention

Drug:
• Oral MRT-2359
Orally administered tablets of MRT-2359.
• Oral MRT-2359
Orally administered tablets of MRT-2359.
• Oral MRT-2359
Orally administered tablets of MRT-2359.
• Oral MRT-2359
Orally administered tablets of MRT-2359.
• Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.
• Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Indiana University	Bloomington	Indiana
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists Research Institute	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Lake Mary	Florida
United States	University of Kansas Cancer Center	Lawrence	Kansas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University Irving Medical Centre	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Washington University	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Monte Rosa Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)		24 months
Secondary	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, AUC0inf, mean residence time, accumulation ratio, etc.		28 days
Secondary	Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DCR		24 months
Secondary	Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PFS		24 months
Secondary	Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as OS		24 months
Secondary	Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PSA response		24 months