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

Trial Summary

What is the purpose of this trial?

This study is to assess the MTD and RP2D of NM6603 in adult patients with advanced solid tumors.

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.

What data supports the effectiveness of the drug NM6603 for cancer treatment?

Research on similar treatments shows that targeting the p53 pathway, which is often mutated in cancers, can be effective. For example, the small-molecule NSC59984 restores normal p53 function and activates p73, leading to cancer cell death with minimal harm to normal cells. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Manipulation of the tumor suppressor p53 for potentiating cancer therapy. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The p53-Mdm2 pathway: targets for the development of new anticancer therapeutics. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

P63 and P73 Activation in Cancers with p53 Mutation. [2022]

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

Phase I trial using patupilone (epothilone B) and concurrent radiotherapy for central nervous system malignancies. [2012]

5. United States 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. [2022]