NM6603 for Cancer

Recruiting at 3 trial locations

Overseen By COO

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NucMito Pharmaceuticals Co. Ltd.

Must not be taking: CYP1A2, CYP3A4, Torsade drugs

Disqualifiers: End organ failure, Other malignancy, ECG abnormalities, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called NM6603 for individuals with advanced solid tumors, aiming to determine the safest and most effective dose. Researchers focus on patients who have tried other treatments without success and whose tumors continue to grow. Those with solid tumors unresponsive to standard treatments and experiencing disease progression might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain drugs that affect heart rhythm or specific liver enzymes. If you're on these, you may need to stop them for a period before joining the trial.

Is there any evidence suggesting that NM6603 is likely to be safe for humans?

Research shows that NM6603 is undergoing safety testing in people with advanced solid tumors. Early results from one study indicated that NM6603 is generally well-tolerated. The study aims to determine the optimal dose of NM6603 that patients can take without serious side effects. As a phase 1 trial, this marks the first time NM6603 is tested in humans. While the treatment is closely monitored, information on its safety remains limited. Participants might experience some side effects, but researchers are actively working to understand and manage these. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional cancer treatments that often involve intravenous chemotherapy, NM6603 is taken orally, offering a more convenient option for patients. Researchers are excited about NM6603 because it introduces a new mechanism of action that targets cancer cells in a novel way, potentially leading to fewer side effects and improved patient outcomes. Additionally, by being administered daily in 28-day cycles, it allows for a more consistent delivery of medication, which may enhance its effectiveness compared to current therapies that require less frequent dosing.

What evidence suggests that NM6603 might be an effective treatment for cancer?

Research shows that NM6603, the investigational treatment in this trial, targets a protein called RXR-alpha, which contributes to cancer cell growth. Researchers are testing this treatment for its effectiveness against solid tumors, such as those in breast and liver cancers. NM6603 blocks an enzyme called topoisomerase, which cancer cells require to copy their DNA and multiply. Early studies have shown that drugs like NM6603 can slow or stop cancer cell growth. Although NM6603 remains in early human testing, its mechanism suggests it could be a promising option for treating advanced cancers. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have progressed despite previous treatments can join this trial. They must be over 18, able to swallow pills, and have a life expectancy of at least 12 weeks. Key health requirements include good kidney function, no serious urine test issues, an ECOG performance status of 0-2 (which measures how cancer affects daily living abilities), and adequate bone marrow reserve and liver function. Women who can get pregnant and men must agree to use birth control during the study.

Inclusion Criteria

Patients must have measurable disease based on RECIST v1.1

My cancer diagnosis was confirmed through tissue or cell testing.

I can take care of myself and perform daily activities.

Exclusion Criteria

Have abnormalities in the 12-lead ECG that in the opinion of the Investigator increase the risk of participating in the study (e.g., sinus rhythm with PR interval > 240 ms or second degree or higher AV block, confirmed by a repeat ECG)

Have ECG evidence of complete left bundle branch block or ventricular pacing

I am mentally and physically capable of participating in a clinical trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

NM6603 is administered orally every day in 28-day cycles to determine the maximum tolerated dose

28 days per cycle

Treatment

NM6603 is administered once daily in Part 1 and twice daily in Part 2 to evaluate safety, tolerability, and pharmacokinetics

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NM6603

Trial Overview The trial is testing NM6603's maximum tolerated dose (MTD) and recommended phase two dose (RP2D) in patients with advanced solid tumors. The goal is to find out the highest dose patients can take without severe side effects and the optimal dose for further studies.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 1 Intervention

NM6603, administered orally every day in 28-day cycles

Who Is Running the Clinical Trial?

NucMito Pharmaceuticals Co. Ltd.

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

The tumor suppressor p53 plays a crucial role in protecting cells from DNA damage, but many tumor cells disable its function through mutations, leading to cancer progression.

Therapeutic strategies targeting the p53 pathway, such as rescuing mutant p53 function and inhibiting its negative regulator Mdm2, show promise in treating cancers with p53-related abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The p53-Mdm2 pathway: targets for the development of new anticancer therapeutics. Zheleva, DI., Lane, DP., Fischer, PM.[2019]

The p53 family, which includes p53, p63, and p73, plays a crucial role in tumor suppression, but p53 is particularly prone to mutations in cancers, leading to a loss of its protective function.

Potential therapies targeting p63 and p73 activators could serve as effective anti-cancer strategies by compensating for the loss of function in mutant p53, especially in cases with gain-of-function mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P63 and P73 Activation in Cancers with p53 Mutation. Cai, BH., Hsu, YC., Yeh, FY., et al.[2022]

In a Phase I study involving 14 patients with recurrent gliomas and brain tumors, patupilone combined with radiotherapy was found to be well tolerated, establishing a maximal tolerated dose of 8 mg/m² every 3 weeks.

The study identified one dose-limiting toxicity (pneumonia) at 8 mg/m² and two severe toxicities (renal failure and pulmonary hemorrhage) at 10 mg/m², indicating that while patupilone is safe, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial using patupilone (epothilone B) and concurrent radiotherapy for central nervous system malignancies. Fogh, S., Machtay, M., Werner-Wasik, M., et al.[2012]

The tumor suppressor p53 plays a crucial role in managing cellular responses to stress, and its inactivation can lead to cancer development, making it a key target for cancer therapies.

Various strategies are being explored to activate or restore p53 functions, including gene therapy and manipulation of p53 regulators, with some approaches already in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulation of the tumor suppressor p53 for potentiating cancer therapy. Haupt, S., Haupt, Y.[2022]

The small molecule NSC59984 effectively targets and depletes mutant p53 proteins, restoring wild-type p53 signaling in colorectal cancer cells, which is crucial since over 50% of human cancers have p53 mutations.

NSC59984 induces cell death in mutant p53-expressing cancer cells with minimal toxicity to normal cells and shows potential to enhance the effectiveness of existing treatments, like CPT11, while inhibiting tumor growth in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53. Zhang, S., Zhou, L., Hong, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06046066

A Phase 1 Study of NM6603 in Advanced Solid Tumors NM6603 is an orally available investigational small molecule indicated for the treatment of solid malignancies including, but not limited to breast, liver, ...

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/rxr-alpha-variant-targeting-agent-nm6603

Clinical Trials Using RXR-alpha Variant-targeting Agent ... NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying rxr-alpha variant-targeting agent nm6603.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10609717/

Topoisomerase Inhibitors: Promising Anti-Cancer Agents This review emphasizes the importance of topoisomerase inhibitors as marketed, clinical and preclinical anti-cancer medications.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8198243/

Emerging Insights: Targeted Therapy-Tolerant Persister Cells In this review, we will discuss insights into mechanisms and vulnerabilities of these cells revealed by recent in vitro, in vivo, and clinical studies. Abstract.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169409X21002830

Nanodelivery of CRISPR/Cas9 for Cancer Treatment For anti-tumor study, the drug loaded micelles shown significant increase of PTX in tumor and improvement of PTX pharmacokinetics, inducing complete tumor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06046066

A Phase 1 Study of NM6603 in Advanced Solid Tumors This is a Phase 1, first-in-human, multicenter, open label, 3+3 dose escalation study designed to evaluate the safety profile, the maximum tolerated dose (MTD),

7. allclinicaltrials.com allclinicaltrials.com/study/NCT06046066

A Phase 1 Study of NM6603 in Advanced Solid Tumors This study is to assess the MTD and RP2D of NM6603 in adult patients with advanced solid tumors. .

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11674295/

Small Molecule with Big Impact: Metarrestin Targets the ... The first part of the Phase I trial intends to assess the safety of the compound in up to 24 adults with solid tumors of any type that have ...