AMT-116 for Cancer

Recruiting in Cary (>99 mi)

+10 other locations

Overseen By Juanjuan Zhu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Multitude Therapeutics Inc.

Disqualifiers: CNS metastasis, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that you should not have had systemic anti-neoplastic therapy within five half-lives or 21 days before the first dose of the trial medication.

What safety data exists for AMT-116 in humans?

Auron Misheil therapy (AMT) has been studied for safety in a phase I trial with healthy male subjects, showing it is generally safe and well-tolerated in a controlled environment. ^{1 2 3 4 5}

How is the drug AMT-116 different from other cancer treatments?

AMT-116 is unique because it may involve a novel approach or mechanism not typically used in standard cancer treatments, such as targeting specific molecular abnormalities or survival mechanisms in cancer cells. This could make it different from traditional chemotherapy or other existing therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase 2 Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-116, in Patients with Advanced Solid Tumors

Research Team

Jermaine Coward

Principal Investigator

ICON Cancer Centre

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors who've tried at least one systemic therapy and have no standard treatment options left, or can't tolerate them. They should have a measurable tumor, be in good physical condition (ECOG 0-1), and agree to use contraception. It's not specified who cannot join.

Inclusion Criteria

My cancer has worsened after treatment and I can't undergo standard therapy.

Patients must have at least one measurable lesion as per RECIST version 1.1.

I have an advanced cancer that cannot be removed by surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of AMT-116 to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Up to 24 months

Follow-up

Participants are monitored for safety, tolerability, and anti-tumor activity after treatment

4-8 weeks

Treatment Details

Interventions

• AMT-116

Trial Overview AMT-116 is being tested to find the highest dose patients can take without serious side effects (MTD/RP2D). The study will also look at how safe it is, how well it works against cancer, how the body processes it, and if it causes any immune reactions.

Participant Groups

Group I: AMT-116 Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Multitude Therapeutics Inc.

Lead Sponsor

Trials

6

Recruited

440+

Findings from Research

A study analyzing 4,339 adverse events (AEs) associated with radium-223 from the Eudra-Vigilance database found that the most common AEs were hematological, general, and gastrointestinal disorders, with over 90% classified as serious and 8% fatal.

Older patients (over 85 years) treated with radium-223 showed a higher risk of cardiac, infectious, and metabolic disorders compared to younger patients, indicating the need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. Tema, G., Lombardo, R., Voglino, O., et al.[2021]

A study involving 52 patients from 2019 to 2021 highlighted the importance of active pharmacovigilance in monitoring adverse drug reactions (ADRs) for oral antineoplastic agents, which are often used despite having limited safety data.

The study found that while hematological disorders were the most common ADRs reported, only four patients discontinued treatment due to toxicity, indicating that the active monitoring model helped in managing adverse events effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active Pharmacovigilance Study: A Follow-Up Model of Oral Anti-Cancer Drugs under Additional Monitoring. Carvalho da Silva, SP., Jesus, M., Roque, F., et al.[2023]

In a study of 1052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen-deprivation therapy significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus ADT.

While apalutamide exposure did not correlate with improved survival outcomes, higher exposure levels were linked to an increased risk of skin rash and pruritus, suggesting that dose adjustments may be beneficial to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. T'jollyn, H., Ackaert, O., Chien, C., et al.[2022]

In a study involving 385 patients with non-castrate metastatic prostate cancer, it was found that physicians significantly under-reported adverse symptoms related to androgen deprivation therapy (ADT), with agreement rates for common symptoms like hot flushes and fatigue being only around 50-64%.

The failure of physicians to report patients' most disturbing symptoms ranged from 50.8% to 89.5%, highlighting the importance of incorporating patients' self-reports in clinical trials to better assess treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). Gravis, G., Marino, P., Joly, F., et al.[2019]

Auron Misheil therapy (AMT) was found to be well tolerated in a phase I study involving 24 healthy male volunteers, with no severe adverse events reported, indicating a good safety profile.

The study provided important pharmacokinetic and pharmacodynamic data for AMT, supporting its potential for further investigation as a supportive care option in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial assessing the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of single-dose Auron Misheil therapy in healthy male subjects. Scheele, J., Diergarten, K., Drevs, J., et al.[2013]

Current standard treatment for acute myeloid leukaemia (AML) does not include maintenance therapy, which is used in other types of leukaemia to prolong responses and improve cure rates.

Although maintenance chemotherapy has not shown benefits in AML, new strategies like immunotherapy, demethylating agents, and targeted therapies are being tested and show promise for improving outcomes in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for maintenance therapy in acute myeloid leukaemia? Baer, MR.[2009]

In younger patients with acute myeloid leukemia (AML), combination chemotherapy using anthracycline and cytarabine has shown very good disease control, especially with recent trials suggesting that increasing the dose of anthracycline during induction therapy can enhance outcomes.

While intensive postremission therapy has been effective in improving survival rates, the addition of the targeted therapy gemtuzumab ozogamicin has not led to better results, indicating a need for further research into newer agents that target specific molecular abnormalities in leukemic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New trends in the standard of care for initial therapy of acute myeloid leukemia. Fernandez, HF.[2016]

In a trial involving patients with acute myeloid leukemia (AML), a single course of consolidation therapy with high-dose cytarabine and amsacrine or allogeneic bone marrow transplantation (alloBMT) resulted in better event-free survival (EFS) compared to lengthy maintenance therapy, with EFS rates of 27% for consolidation and 16% for maintenance.

AlloBMT showed a significantly better EFS (42%) compared to maintenance therapy (14%), although it was not significantly different from consolidation therapy (30%), highlighting the need for further studies to confirm these findings and explore safer alternatives for older patients due to high mortality rates associated with consolidation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varying intensity of postremission therapy in acute myeloid leukemia. Cassileth, PA., Lynch, E., Hines, JD., et al.[2021]

In a study of 52 transplant-ineligible AML patients, those who received oral maintenance chemotherapy after achieving remission had a median overall survival of 43 months compared to 19 months in the control group, although this difference was not statistically significant (P = 0.202).

Maintenance chemotherapy was identified as an independent prognostic factor for better overall survival and leukemia-free survival, particularly benefiting older patients, those with intermediate or unfavorable cytogenetics, and those with lower initial blast counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation. Choi, YW., Jeong, SH., Ahn, MS., et al.[2018]

Recent studies indicate that maintenance therapy for acute myeloid leukemia (AML) can be beneficial, particularly for high-risk patients or those with measurable residual disease (MRD), as shown in randomized trials.

The introduction of modern targeted agents, such as oral hypomethylating agents and immune checkpoint inhibitors, has renewed interest in maintenance therapy, emphasizing the need for standardized MRD measurement techniques in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Shallis, RM., Podoltsev, NA.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Active Pharmacovigilance Study: A Follow-Up Model of Oral Anti-Cancer Drugs under Additional Monitoring. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). [2019]

5. England pubmed.ncbi.nlm.nih.gov

A phase I trial assessing the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of single-dose Auron Misheil therapy in healthy male subjects. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Is there a role for maintenance therapy in acute myeloid leukaemia? [2009]

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

New trends in the standard of care for initial therapy of acute myeloid leukemia. [2016]

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

Varying intensity of postremission therapy in acute myeloid leukemia. [2021]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation. [2018]

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

Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. [2023]