MRT-2359 for Solid Tumors

Recruiting at 24 trial locations

Overseen By Monte Rosa Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Monte Rosa Therapeutics, Inc

Must be taking: Fulvestrant, Enzalutamide

Must not be taking: Bisphosphonates, Denosumab, Steroids, others

Disqualifiers: Malabsorption, CNS involvement, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MRT-2359, designed to help individuals with certain solid tumors, such as non-small cell lung cancer, small cell lung cancer, and some types of breast and prostate cancers. The research aims to determine the safety, tolerability, and optimal dosage of this treatment. Suitable candidates for this trial have previously treated solid tumors or lymphoma and lack other standard treatment options. Additionally, their tumors may exhibit specific gene characteristics, such as L-MYC or N-MYC amplification. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chemotherapy, radiation, or biological cancer therapy, at least 21 days before starting the study treatment. However, if you have prostate cancer, you can continue therapies to maintain low testosterone levels, and pre-menopausal women with hormone-dependent breast cancer can continue therapies for ovarian function suppression.

Is there any evidence suggesting that MRT-2359 is likely to be safe for humans?

Research has shown that MRT-2359 has a good safety record in studies involving various solid tumors. Patients with non-small cell lung cancer (NSCLC) and other tumors driven by the MYC gene tolerated MRT-2359 well, even after many previous treatments. The studies demonstrated that the drug was easy for the body to handle and had the desired effects.

For prostate cancer, researchers are testing MRT-2359 with enzalutamide, a drug already used for this cancer. Early safety checks for this combination are ongoing, ensuring that any side effects receive close monitoring.

In summary, MRT-2359 has been well-tolerated in early studies across various cancer types. While these results are encouraging, ongoing research aims to confirm the safety and effectiveness of MRT-2359 in larger patient groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for solid tumors?

Researchers are excited about MRT-2359 because it targets the L-MYC and N-MYC genes, which play a crucial role in the growth of certain solid tumors. Unlike standard treatments like chemotherapy, which attacks both healthy and cancerous cells, MRT-2359 offers a more precise approach by focusing on specific genetic amplifications found in some cancers, potentially reducing side effects. Additionally, the versatility of MRT-2359 is noteworthy as it is being tested across various cancers, including small cell lung cancer (SCLC), prostate cancer, and breast cancer, often in combination with other drugs to enhance effectiveness. This targeted strategy provides hope for improved outcomes and personalized therapy options for patients with these aggressive cancers.

What evidence suggests that MRT-2359 could be an effective treatment for solid tumors?

Research has shown that MRT-2359 could help treat various solid tumors, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In this trial, participants will join different treatment arms based on their cancer type. Studies have found that MRT-2359 is generally safe and works by breaking down a protein called GSPT1, present in cancer cells. Early tests showed MRT-2359 was particularly effective in tumors with high levels of L-MYC or N-MYC, common in some lung cancers. One arm of this trial will explore MRT-2359 combined with enzalutamide for patients with castration-resistant prostate cancer. Another arm will investigate the combination of MRT-2359 with fulvestrant for hormone receptor-positive, HER2-negative breast cancer. Overall, MRT-2359 shows promise for treating several challenging cancers. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with certain advanced cancers (like lung cancer, neuroendocrine carcinoma, or lymphoma) who've tried other treatments without success. They must be expected to live at least 3 months, be able to perform daily activities with minimal assistance, and use birth control. People can't join if they've had recent cancer treatments that haven't worn off yet or have serious health issues like active infections or heart disease.

Inclusion Criteria

My advanced cancer has no more standard treatment options.

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

I am expected to live more than 3 months and can care for myself.

Exclusion Criteria

I have had pneumonitis treated with steroids.

Be pregnant or breastfeeding

I have not had a live vaccine in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Participants receive escalating doses of MRT-2359 to determine safety, tolerability, and maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

8-12 weeks

Phase 2 Expansion

Participants are enrolled based on molecular biomarkers stratification or selection to assess preliminary anti-tumor activity of MRT-2359

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRT-2359

Trial Overview The trial is testing MRT-2359 pills on patients with specific cancers. It's in two parts: first finding the highest dose people can take without bad side effects (Phase 1), then seeing how well it works at that dose (Phase 2). The focus is also on genetic markers related to the cancer.

How Is the Trial Designed?

Group I: Phase 2 Expansion - SCLC Experimental Treatment 1 Intervention

Patients with SCLC

Group II: Phase 2 Expansion - Prostate Cancer Experimental Treatment 1 Intervention

Patients with prostate cancer in combination with enzalutamide

Group III: Phase 2 Expansion - NSCLC Experimental Treatment 1 Intervention

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

Group IV: Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors Experimental Treatment 1 Intervention

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

Group V: Phase 2 Expansion - HR-positive, HER2-negative breast cancer Experimental Treatment 1 Intervention

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

Group VI: Phase 1 Dose Escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Monte Rosa Therapeutics, Inc

Lead Sponsor

Trials

2

Recruited

250+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05546268?term=NCT05546268&rank=1

Study of Oral MRT-2359 in Selected Cancer Patients HR-positive, HER2-negative breast cancer - MRT-2359 in combination with fulvestrant; Non-neuroendocrine prostate cancer - MRT-2359 in combination with ...

2. ir.monterosatx.com ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-provides-development-progress-update

Release Details Results from dose escalation arms of Phase 1/2 study of MRT-2359 demonstrated a favorable safety profile and targeted levels of GSPT1 degradation.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8391338/

Efficacy of Fulvestrant in Women with Hormone-Resistant ... Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival ...

4. go.drugbank.com go.drugbank.com/conditions/DBCOND0148150

HR+/HER2- Breast Cancer (DBCOND0148150) Associated Data ; NCT06705504. A Real-world Study of Effectiveness and Safety in HR+/HER2- Breast Cancer Patients Treated With Ribociclib or Alpelisib, No drug ...

5. pfizerclinicaltrials.com pfizerclinicaltrials.com/find-a-trial/nct07062965-breast-cancer-trial

Clinical Trial for Breast Cancer. Cancer cells that are HER2-negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05546268

Study of Oral MRT-2359 in Selected Cancer Patients Phase 2 Expansion - HR-positive, HER2-negative breast cancer. Patients with HR-positive, HER2-negative breast cancer in combination with fulvestrant.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40755830/

Capivasertib/Fulvestrant: HR+/HER2- Breast Cancer Treatment Notably, Capivasertib plus Fulvestrant received Food and Drug Administration (FDA) approval in 2023 for ER-positive/HER2-negative breast cancer ...