NG-350A + Chemoradiotherapy for Rectal Cancer

(FORTRESS Trial)

Recruiting at 6 trial locations

Overseen By Vice President Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Akamis Bio

Must not be taking: Immunosuppressants, Anti-CD40 antibody

Disqualifiers: Recurrent cancer, Metastatic disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NG-350A, an experimental therapy, combined with chemoradiotherapy for individuals with locally advanced rectal cancer. The goal is to determine if this combination can prevent the cancer from returning, either locally or in other parts of the body. The study targets individuals diagnosed with rectal cancer that hasn't spread extensively and who have a good chance of responding to intensive treatment. Participants must have a specific type of cancer cell status and be able to tolerate the study's treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you need to stop your current medications. However, if you are on systemic immunosuppressive therapy or have had other anti-cancer treatments in the past 12 months, you may not be eligible to participate.

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

Research has shown that NG-350A appears safe so far. One study found that NG-350A targets cancer cells without harming normal cells, suggesting it might be easier for patients to tolerate. The FDA granted it fast track status, often given to treatments with potential benefits and manageable safety risks.

As NG-350A is in a phase 1 trial, it remains in the early stages of testing. This phase primarily focuses on safety, so only a small number of participants have been tested. However, the treatment's ability to target cancer cells indicates promising safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for rectal cancer?

Unlike the standard treatments for rectal cancer, which typically involve a combination of surgery, chemotherapy, and radiation, NG-350A is unique because it is an investigational drug that works by stimulating the immune system to attack cancer cells more effectively. Most current treatments focus on directly killing cancer cells, but NG-350A aims to enhance the body’s natural defenses. This novel approach has the potential to improve outcomes by targeting cancer cells with precision while sparing healthy tissues, which is why researchers are particularly excited about its possibilities.

What evidence suggests that NG-350A plus chemoradiotherapy could be effective for rectal cancer?

Research has shown that NG-350A, administered alongside chemoradiotherapy (CRT) in this trial, could be a promising treatment for advanced rectal cancer. A previous study confirmed that NG-350A effectively reaches tumors and shows signs of multiplying and activating important genes to combat cancer cells. The FDA granted NG-350A fast track status, indicating its potential to improve treatment outcomes for patients. This status suggests that NG-350A might become an important option for rectal cancer therapy, especially when combined with traditional treatments like chemotherapy and radiation. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced rectal cancer who are not pregnant or breastfeeding, can perform daily activities (ECOG 0-1), agree to use contraception, and have stable vital organ functions. It's specifically for those with a certain type of genetic status in their cancer cells (MSS/pMMR) and who are chosen for neoadjuvant chemoradiotherapy.

Inclusion Criteria

I have signed a consent form to participate.

I am not pregnant or breastfeeding.

I agree to follow the study's birth control requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NG-350A in combination with chemoradiotherapy for locally advanced rectal cancer

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• NG-350A
• Radiotherapy

Trial Overview The FORTRESS trial tests NG-350A given through IV along with standard chemoradiotherapy, which includes radiation therapy and oral Capecitabine. The goal is to see how well this combination works in treating locally advanced rectal cancer.

How Is the Trial Designed?

Group I: NG-350A plus CRT during a 12-week active study treatment period Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Akamis Bio

Lead Sponsor

Trials

13

Recruited

820+

Published Research Related to This Trial

For clinically resectable rectal cancer, two main treatment approaches exist: surgery followed by postoperative therapy for certain tumor stages, or preoperative therapy followed by surgery and additional postoperative therapy for more advanced tumors.

New chemotherapeutic agents are being tested in combination with pelvic radiation, particularly in preoperative settings, showing promising early results with higher complete response rates compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality therapy of resectable rectal cancer: current approaches. Minsky, BD.[2005]

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

In a review of 21 randomized controlled trials involving 9040 patients with nonmetastatic prostate cancer, it was found that acute adverse events (AEs) were primarily reported by clinicians, while patient-reported outcomes (PROs) were underutilized, especially for late AEs.

The study highlights a gap in incorporating patient perspectives in reporting AEs related to radical radiation therapy, suggesting a need for standardized PRO assessments to better capture patient experiences and improve treatment evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and Late Adverse Events Associated With Radical Radiation Therapy Prostate Cancer Treatment: A Systematic Review of Clinician and Patient Toxicity Reporting in Randomized Controlled Trials. Holch, P., Henry, AM., Davidson, S., et al.[2022]

In a study of 100 patients undergoing chemoradiotherapy for localized anal cancer, patient-reported outcomes (PROs) indicated a higher incidence of acute toxicity compared to physician-assessed toxicity (CTCAE), highlighting the importance of incorporating PROs in evaluating treatment effects.

Proton therapy demonstrated superior dosimetric planning compared to IMRT and VMAT, suggesting it may reduce radiation exposure to surrounding healthy tissues, potentially leading to lower toxicity in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. Kronborg, C., Serup-Hansen, E., Lefevre, A., et al.[2019]

Citations

1. onclive.com onclive.com/view/fda-grants-fast-track-status-to-ng-350a-for-pmmr-locally-advanced-rectal-cancer

FDA Grants Fast Track Status to NG-350A for pMMR ... NG-350A has been awarded fast track designation from the FDA for rectal cancer and is under further evaluation in the FORTRESS trial.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11481156/

First-in-human clinical outcomes with NG-350A, an anti- ... This phase 1a study provided initial proof-of-mechanism for NG-350A, with strong evidence of tumor delivery, viral replication and transgene expression.

3. targetedonc.com targetedonc.com/view/fda-grants-fast-track-to-ng-350a-for-pmmr-rectal-cancer

FDA Grants Fast Track to NG-350A for pMMR Rectal Cancer The FDA fast-tracks NG-350A, an innovative immunotherapy for advanced rectal cancer, aiming to enhance treatment options and patient outcomes.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06459869

NG-350A Plus Chemoradiotherapy for Locally Advanced ... The FORTRESS trial (NG-350A-03) is an open-label, single-arm, and multicentre trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients ...

5. cancernetwork.com cancernetwork.com/view/fda-grants-fast-track-designation-to-ng-350a-for-pmmr-rectal-cancer

FDA Grants Fast Track Designation to NG-350A for pMMR ... Akamis Bio receives FDA fast track designation for NG-350A for the treatment of mismatch repair-proficient locally advanced rectal cancer. News ...

6. isrctn.com isrctn.com/ISRCTN12595783

NG-350A plus chemoradiotherapy for locally advanced ... NG-350A can multiply in and kill cancer cells, but it is not expected to have an effect on normal cells. Who can participate? Patients with locally advanced ...