REM-422 for Advanced Cancer

Recruiting at 7 trial locations

Overseen By Remix Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Remix Therapeutics

Must not be taking: CYP3A inhibitors, CYP3A inducers, Antacids

Disqualifiers: Active infection, HIV, Hepatitis, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of an experimental drug, REM-422, which targets and aims to shrink tumors in people with advanced Adenoid Cystic Carcinoma (ACC), a rare cancer. Participants will receive different doses to determine the optimal balance of safety and effectiveness. This trial suits those with ACC that has spread or worsened, who experience symptoms like pain or difficulty breathing, and who can swallow oral medications.

As a Phase 1 trial, participants will be among the first to receive this new treatment, helping researchers understand its effects in people.

Will I have to stop taking my current medications?

The trial requires that participants stop using certain medications, such as strong CYP3A inhibitors or inducers, drugs that reduce stomach acid, and any prohibited medication at least 1 week before starting REM-422. If you are on these medications, you may need to stop or adjust them before joining the trial.

Is there any evidence suggesting that REM-422 is likely to be safe for humans?

Research has shown that REM-422 has promising safety results for people with adenoid cystic carcinoma (ACC). In earlier studies, REM-422, an oral treatment targeting mRNA, proved to be safe, meaning patients tolerated the treatment well. The doses tested did not cause severe side effects, which is encouraging for those considering joining a trial. Although still in the early stages, the findings suggest that REM-422 could be a safe option for people with this type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced cancer, which often rely on chemotherapy or targeted therapies, REM-422 offers a unique approach as it is delivered orally in capsule form. This method of administration can potentially enhance patient convenience and compliance. Researchers are particularly excited about REM-422 because it involves a novel dose escalation strategy to determine the safest and most effective dosage, potentially optimizing therapeutic outcomes. Additionally, REM-422 aims to establish a recommended phase 2 dose that could lead to more personalized treatment strategies tailored to patient-specific needs.

What evidence suggests that REM-422 might be an effective treatment for advanced Adenoid Cystic Carcinoma?

Research shows that REM-422 targets and breaks down MYB mRNA, a type of genetic material that aids the growth of certain cancer cells. In studies with patients who have Adenoid Cystic Carcinoma (ACC), REM-422 has shown promise by lowering levels of MYB mRNA and its related proteins. This is crucial because MYB often lacks control in ACC, promoting cancer growth. REM-422 has consistently worked in the body at different doses, indicating its potential effectiveness. These early findings suggest that REM-422 could be an effective treatment option for people with advanced ACC. Participants in this trial will receive REM-422 in a dose escalation phase to determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), followed by a dose expansion phase at the identified RP2D. ^{2 5 6 7 8}

Who Is on the Research Team?

Christopher Bowden, MD

Principal Investigator

Remix Therapeutics

Are You a Good Fit for This Trial?

Adults with advanced Adenoid Cystic Carcinoma (ACC) who can consent, swallow pills, and have proper organ function. They must not have had recent non-study cancer treatments or major surgeries and should show disease progression. Women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

Be able to provide informed consent.

My cancer is advanced or has spread to other parts of my body.

My cancer has worsened or I have symptoms like pain or trouble breathing, and I haven't tolerated other treatments well.

Exclusion Criteria

Participants receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.

Unwillingness or inability to follow protocol requirements.

I need or will need daily corticosteroid treatment equivalent to 10 mg of prednisone or more.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

Until MTD/RP2D is determined

Dose Expansion

Participants receive REM-422 at the identified RP2D to further evaluate safety and anti-tumor activity

Until disease progression, therapy intolerance, or participant withdrawal

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Safety evaluation will continue until 30 days after last administration of REM-422

What Are the Treatments Tested in This Trial?

Interventions

• REM-422

Trial Overview The study tests REM-422's safety and effectiveness against ACC tumors. Participants will take this MYB mRNA degrader orally, with the trial having two phases: dose escalation for those showing symptoms or stable disease on intolerable treatment, and dose expansion for measurable progressing disease.

How Is the Trial Designed?

Group I: REM-422 Experimental Treatment 1 Intervention

* Dose Escalation: Participants will receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)-422, oral capsule administered once daily * Dose Expansion: Participants will receive REM-422 at the identified RP2D * Treatment will continue until disease progression, therapy intolerance, or participant withdrawal * Safety evaluation will continue until 30 days of last administration of REM-422

REM-422 is already approved in United States for the following indications:

Approved in United States as REM-422 for:

• Adenoid Cystic Carcinoma (ACC)
• Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Remix Therapeutics

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

The use of antisense v-myb' RNA in K562 human leukemia cells significantly reduced cell proliferation by 50% and promoted differentiation towards myelomonocytic lineage, indicating a potential therapeutic strategy for leukemia.

In contrast, the sense v-myb' RNA did not affect cell proliferation or differentiation, highlighting the specific role of antisense RNA in regulating the c-myb gene and its impact on leukemia cell behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the antisense v-myb' expression on K562 human leukemia cell proliferation and differentiation. Kamano, H., Ohnishi, H., Tanaka, T., et al.[2019]

The protooncogene c-myb is overexpressed in certain human colon carcinoma cell lines, particularly in the doxorubicin-resistant LoVo/Dx cells, indicating a potential link between c-myb expression and drug resistance.

Inhibition of c-myb using antisense oligodeoxynucleotides effectively reduced cell proliferation in c-myb expressing cell lines, suggesting that targeting c-myb could be a therapeutic strategy for treating colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of proliferation by c-myb antisense oligodeoxynucleotides in colon adenocarcinoma cell lines that express c-myb. Melani, C., Rivoltini, L., Parmiani, G., et al.[2013]

The study found that c-myb antisense oligodeoxynucleotides significantly inhibited the growth of leukemic cells, affecting 78% of acute myelogenous leukemia cases and 80% of chronic myelogenous leukemia cases in blast crisis, while sparing normal hematopoietic progenitor cells.

This differential sensitivity suggests that targeting c-myb could be a promising strategy for leukemia therapy, potentially allowing for the elimination of leukemic cells without harming normal cells, which could be useful for treatments like ex vivo bone marrow purging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normal and leukemic hematopoietic cells manifest differential sensitivity to inhibitory effects of c-myb antisense oligodeoxynucleotides: an in vitro study relevant to bone marrow purging. Calabretta, B., Sims, RB., Valtieri, M., et al.[2022]

Targeting the c-Myb proto-oncogene in acute lymphoblastic leukemia (ALL) can decrease the viability of leukemic cells and increase their sensitivity to chemotherapy, suggesting it could enhance treatment effectiveness.

In a mouse model, inhibiting c-Myb not only delayed leukemia onset but also indicated that combining c-Myb suppression with existing therapies could reduce treatment-related toxicities and improve survival rates for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of c-Myb in the survival of pre B-cell acute lymphoblastic leukemia and leukemogenesis. Sarvaiya, PJ., Schwartz, JR., Hernandez, CP., et al.[2021]

Bcr-TMP is a newly identified MYB-inhibitory compound that effectively reduces the viability of acute myeloid leukemia (AML) cell lines at nanomolar concentrations by inducing MYB degradation and disrupting its interaction with the co-activator p300.

This compound not only down-regulates MYB target genes but also shows stronger anti-proliferative effects on MYB-addicted cancer cells compared to non-cancerous cells, suggesting its potential as a targeted therapy for malignancies like AML and adenoid cystic carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. Yusenko, MV., Biyanee, A., Frank, D., et al.[2022]

The MYB transcription factor is crucial for the development of various cancers, including leukemia and breast cancer, making it a promising target for new cancer therapies.

Recent advancements in understanding MYB's regulatory mechanisms have led to the exploration of innovative therapeutic strategies, such as RNA interference and low-molecular-weight compounds, which aim to inhibit MYB and its co-regulators more effectively than previous antisense therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reassessing the Potential of Myb-targeted Anti-cancer Therapy. Liu, X., Xu, Y., Han, L., et al.[2020]

MYB is identified as a promising drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC), with recent studies showing that it can be effectively inhibited by low molecular weight compounds.

The proteasome inhibitor oprozomib was found to significantly inhibit MYB activity and reduce the proliferation of AML and ACC cells, suggesting a novel therapeutic approach by targeting MYB through proteasome inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner. Yusenko, MV., Biyanee, A., Andersson, MK., et al.[2022]

Citations

1. remixtx.com remixtx.com/remix-therapeutics-announces-positive-preliminary-data-from-phase-1-study-of-rem-422-in-patients-with-adenoid-cystic-carcinoma-at-the-2025-aacr-nci-eortc-international-conference-on-molecular/

Remix Therapeutics REM-422 demonstrated linear pharmacokinetics in blood across all dose levels accompanied by a reduction of MYB mRNA and protein levels in ACC ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06118086

Study of REM-422 in Patients With Recurrent or Metastatic ... This is a Phase 1, open-label, non-randomized, multicenter study investigating REM-422, a potent, selective, and oral small molecule mRNA degrader that ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/c-myb-mrna-degrader-rem-422?pn=1

Clinical Trials Using c-Myb mRNA Degrader REM-422 - NCI Review the clinical trials studying c-myb mrna degrader rem-422 on this list and use the filters to refine the results by age and location.

4. accrf.org accrf.org/wp-content/uploads/2025/02/ENA-2024-MYB-ACC-poster_final.pdf

REM-422, a potent, selective, oral small molecule mRNA ... Recurrent genetic lesions and dysregulation of MYB have been identified in a variety of cancers, including adenoid cystic carcinoma (ACC), acute myeloid.

5. finance.yahoo.com finance.yahoo.com/news/remix-therapeutics-announces-positive-preliminary-140000535.html

Remix Therapeutics Announces Positive Preliminary Data ... REM-422 demonstrated linear pharmacokinetics in blood across all dose levels accompanied by a reduction of MYB mRNA and protein levels in ACC ...

6. remixtx.com remixtx.com/rem-422/

REM-422 Preliminary positive results from the Phase 1 trial of REM-422 in ACC has demonstrated inhibition of MYB mRNA and anti-tumor activity at well-tolerated doses.

7. biospace.com biospace.com/press-releases/remix-therapeutics-announces-positive-preliminary-data-from-phase-1-study-of-rem-422-in-patients-with-adenoid-cystic-carcinoma-at-the-2025-aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics

Remix Therapeutics Announces Positive Preliminary Data ... REM-422 is the first oral mRNA degrader of MYB demonstrating proof-of-mechanism and proof-of-concept in ACC along with a favorable safety ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06297941

Study of REM-422 in Patients With AML or Higher Risk MDS The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk MDS and relapsed/refractory ...