REM-422 for Advanced Cancer

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Remix Therapeutics

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

Disqualifiers: Active infection, HIV, Hepatitis, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing REM-422, an oral medicine, in people with advanced Adenoid Cystic Carcinoma (ACC) that has returned or spread. REM-422 aims to reduce a protein needed for cancer growth by breaking down its mRNA. The study will determine the best dose and evaluate its safety and effectiveness.

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.

What data supports the effectiveness of the drug REM-422 for advanced cancer?

Research shows that targeting the MYB gene, which REM-422 aims to degrade, can reduce cancer cell growth in various cancers like acute myeloid leukemia and adenoid cystic carcinoma. Similar treatments that inhibit MYB have shown promise in reducing cancer cell viability and proliferation. ^{1 2 3 4 5}

What makes the drug REM-422 unique for treating advanced cancer?

REM-422 is unique because it specifically targets and degrades the MYB mRNA, a key factor in the growth of certain cancers, which is a novel approach compared to traditional treatments that may not directly target this transcription factor. ^{1 2 4 6 7}

Research Team

Christopher Bowden, MD

Principal Investigator

Remix Therapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• REM-422 (MYB mRNA degrader)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Remix Therapeutics

Lead Sponsor

Trials

2

Recruited

170+

Findings from Research

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Inhibition of proliferation by c-myb antisense oligodeoxynucleotides in colon adenocarcinoma cell lines that express c-myb. [2013]

3. United States 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. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Role of c-Myb in the survival of pre B-cell acute lymphoblastic leukemia and leukemogenesis. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Reassessing the Potential of Myb-targeted Anti-cancer Therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Effects of the antisense v-myb' expression on K562 human leukemia cell proliferation and differentiation. [2019]