Study of Oral MRT-2359 in Selected Cancer Patients

Monte Rosa Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: Oral MRT-2359

Study type: Interventional

Funder types: Industry

Identifiers

NCT05546268

MRT-2359-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 174 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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174 participants in 6 patient groups

Phase 1 Dose Escalation

Experimental group

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

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Phase 2 Expansion - NSCLC

Experimental group

Description:

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

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Phase 2 Expansion - SCLC

Experimental group

Description:

Patients with SCLC

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

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

Experimental group

Description:

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

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

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

Experimental group

Description:

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

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Phase 2 Expansion - Prostate Cancer

Experimental group

Description:

Patients with prostate cancer in combination with enzalutamide

Treatment:

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359

Drug: Oral MRT-2359