AMB-05X for Colorectal Cancer

Overseen By Van Morris, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Concurrent malignancy, Hepatobiliary disease, Autoimmune disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called AMB-05X, a new potential drug, to determine its effectiveness for people with colorectal cancer (CRC) who show no visible signs of the disease but still have cancer DNA in their blood. The main goal is to assess AMB-05X's effectiveness for those who have completed all standard treatments, such as surgery and chemotherapy, yet still have minimal residual disease (tiny cancer traces) detected by a special blood test. The trial seeks participants diagnosed with adenocarcinoma of the colon or rectum, who have completed their treatments, and have a positive ctDNA test. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other systemic anti-cancer treatments or certain medications like pexidartinib or tyrosine kinase inhibitors within the past 4 weeks.

Is there any evidence suggesting that AMB-05X is likely to be safe for humans?

Research shows that AMB-05X is under investigation as a potential treatment for colorectal cancer. Current studies are examining the safety and tolerability of this treatment for patients. At M.D. Anderson Cancer Center, researchers are assessing whether AMB-05X causes manageable side effects. These studies closely monitor any adverse reactions and how well patients tolerate the treatment. Since AMB-05X is in Phase 2 trials, earlier trials have already provided some safety information. However, more data is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AMB-05X for colorectal cancer because it targets the cancer cells in a novel way, potentially offering benefits over existing treatments like chemotherapy and targeted therapies such as EGFR inhibitors. Unlike standard treatments that often have a wide range of side effects due to their impact on both cancerous and healthy cells, AMB-05X is designed to more precisely attack cancerous cells, which could mean fewer side effects and a better quality of life for patients. Additionally, this new treatment might work in patients who have not responded well to current options, giving hope to those with limited alternatives.

What evidence suggests that AMB-05X might be an effective treatment for colorectal cancer?

Research has shown that AMB-05X, the investigational treatment in this trial, targets a specific protein called CSF1R, which contributes to the growth and spread of cancer cells. Studies suggest that AMB-05X may help control tumors in colorectal cancer (CRC) patients with minimal residual disease after treatment. Early evidence indicates it could help patients remain cancer-free for longer. Researchers hope that AMB-05X will improve overall survival rates for people with CRC. ^{1 2 3 4 5}

Who Is on the Research Team?

Van K. Morris

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with colorectal cancer who have had treatment intended to cure them but still show signs of microscopic residual disease through a positive ctDNA blood test, without any visible disease on scans.

Inclusion Criteria

I've completed all treatments for my stage I-IV colorectal cancer and currently show no signs of the disease.

My blood test for cancer DNA was positive 28 days after finishing all my planned treatments.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

I haven't taken specific medications in the last 4 weeks.

Patients with psychiatric illness/social situations that would limit compliance with study requirements

Exclusion of pregnant women and breastfeeding mothers

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMB-05X for 6 months to determine ctDNA clearance rate

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for disease-free survival (DFS) and overall survival (OS) over 2 years

2 years

What Are the Treatments Tested in This Trial?

Interventions

• AMB-05X

Trial Overview The study tests the effectiveness of AMB-05X in preventing cancer recurrence in patients whose blood tests indicate remaining cancer traces at the molecular level after curative-intent treatments.

How Is the Trial Designed?

Group I: AMB-05X Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 124 colorectal cancer patients treated with the mFOLFOX6 regimen, the most common severe adverse events were neutropenia (40%) and leucopenia (16%), indicating that while the treatment can have significant side effects, it is generally tolerable.

The incidence of adverse events in this Japanese cohort was similar or lower than those reported in Western countries, suggesting that the mFOLFOX6 regimen is manageable in clinical practice and that informed consent forms were updated to better inform patients about potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. Kato, T., Matsunaga, Y., Motokawa, S., et al.[2013]

Aflibercept combined with FOLFIRI significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin, showing median survival of 12.5 months compared to 11.7 months with placebo.

The treatment effect of aflibercept was consistent across various patient subgroups, including those with or without prior bevacizumab treatment, indicating its broad efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Tabernero, J., Van Cutsem, E., Lakomý, R., et al.[2022]

Amonafide, administered at a dose of 300 mg/m2 for five consecutive days, showed no significant anti-tumor activity in 14 patients with recurrent or metastatic colorectal cancer, as there were no observed responses despite some patients having stable disease.

The treatment was associated with notable side effects, particularly neutropenia (Grade 3 or 4 toxicity in 5 out of 14 patients), along with other toxicities like nausea, vomiting, and fever, indicating a need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer. O'Dwyer, PJ., Paul, AR., Hudes, GR., et al.[2020]

In a trial involving 44 patients with advanced colorectal cancer, amonafide was administered at a dose of 300 mg/m2, but it resulted in no complete or partial responses, indicating an overall response rate of 0%.

The treatment caused significant toxicities, with 47% of patients experiencing grade 3 or higher adverse effects, including severe blood cell reductions and other serious conditions, suggesting that while the dose intensity was appropriate, the drug may not be effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of amonafide in advanced colorectal cancer: a SouthWest Oncology Group study. Brown, TD., Goodman, PJ., Fleming, T., et al.[2020]

Aflibercept, when combined with chemotherapy for metastatic colorectal cancer, is associated with a significantly increased risk of antiangiogenic adverse events, including hypertension (44.2% incidence) and proteinuria (31.3% incidence) among 2889 patients from 10 studies.

Compared to control treatments, aflibercept showed a notably higher incidence of severe adverse events, such as grade III/IV hypertension (OR: 7.20) and grade III/IV proteinuria (OR: 5.13), indicating that while it is effective, careful monitoring for these side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis. Ge, P., Han, C., Reyila, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06617858

NCT06617858 | Trial of AMB-05X for Patients With ctDNA ... To investigate the efficacy of AMB-05X in patients with CRC with MRD as determined by a ctDNA(+) blood test and no clinically detectable radiographic disease.

2. onclive.com onclive.com/view/csf1r-blockade-with-amb-05x-may-improve-tumor-control-in-ctdna-crc

CSF1R Blockade With AMB-05X May Improve Tumor ... Exploratory end points include the estimated 2-year disease-free survival and overall survival rates; the pharmacokinetic profile of AMB-05X; ...

3. clinicaltrials.eu clinicaltrials.eu/inn/amb-05x/

Amb-05X – Application in Therapy and Current ... AMB-05X is an investigational drug currently being studied for its potential in treating colorectal cancer (CRC).

4. sigma.larvol.com sigma.larvol.com/product.php?e1=2083&tab=newstrac

AMB-05X News Secondary outcome measures include ORR per modified RECIST and Tumor Volume Score, duration of response, time to response, PRO/QOL (including range of motion, ...

5. withpower.com withpower.com/trial/phase-2-colorectal-carcinoma-crc-1-2025-e72db

AMB-05X for Colorectal Cancer To investigate the efficacy of AMB-05X in patients with CRC with MRD as determined by a ctDNA(+) blood test and no clinically detectable radiographic disease.