Nelitolimod for Colorectal Cancer

Overseen By Micaela Wigfall Maxwell

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwell Health

Must be taking: Chemotherapy

Must not be taking: Immunosuppressants, Immunomodulatory agents

Disqualifiers: Autoimmune disease, Heart failure, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Nelitolimod for colorectal cancer that has spread to the liver. Researchers aim to determine if this drug can enhance the immune system's ability to fight cancer when administered directly to the liver without compromising surgical safety. They will assess the safety and practicality of this approach before surgery in patients with liver-only, resectable metastatic colorectal cancer. Individuals with colorectal cancer that has spread to the liver and remains surgically removable might be suitable candidates. As an Early 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 need to stop taking your current medications, but you cannot be on immunosuppressive agents within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

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

Research has shown that Nelitolimod, administered through pressure-enabled drug delivery (PEDD), is generally well-tolerated by patients with colorectal liver metastases. In earlier studies, patients receiving Nelitolimod via this method found the treatment safe and free from severe side effects. These studies examined the drug's effectiveness on tumors while also emphasizing safety.

Although the treatment remains in early testing stages for colorectal cancer, the safe use of Nelitolimod in other studies is encouraging. Since this trial is in its early phase, the primary goal is to ensure the treatment's safety for people. This phase will help confirm that the treatment does not cause serious health problems and is safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nelitolimod is unique because it activates the immune system differently than standard colorectal cancer treatments like chemotherapy or targeted therapies. Most treatments aim to directly kill cancer cells, but Nelitolimod works by stimulating a part of the immune system called Toll-like receptor 9 (TLR9). This boosts the body's natural ability to fight cancer, potentially leading to fewer side effects and improved outcomes. Researchers are excited about it because this approach could offer a new way to combat cancer that complements existing therapies.

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

Studies have shown that Nelitolimod can boost the body's immune response against tumors. Previous research demonstrated that using a special method called Pressure Enabled Drug Delivery (PEDD) made Nelitolimod more effective at reducing the tumor's ability to weaken the immune system. Other studies have linked Nelitolimod to a noticeable reduction in tumor size in various cancers, suggesting potential benefits for colorectal cancer patients. Although direct data on colorectal cancer is limited, Nelitolimod's mechanism offers hope that it could enhance the body’s natural defenses against the cancer. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with colorectal liver metastases (CRLM). Participants should be candidates for liver resection and must have completed standard chemotherapy. Specific details on inclusion and exclusion criteria are not provided, but typically these would involve factors like overall health status, prior treatments, and absence of conditions that could interfere with the study or patient safety.

Inclusion Criteria

Hematologic parameters defined as: Absolute neutrophil count (ANC) ≥ 1000 cells/mm3, Platelet count ≥ 100,000/mm3, Hemoglobin ≥ 8 g/dL.

Blood chemistry levels defined as: AST, ALT, alkaline phosphatase ≤5 times upper limit of normal (ULN), Total bilirubin ≤2x the ULN. Patients with Gilbert Syndrome should have a serum bilirubin ≤ 4x ULN and a direct bilirubin ≤2x ULN to be eligible.

Anticipated life expectancy greater than 6 months.

Exclusion Criteria

Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, such as rheumatoid arthritis, which in the opinion of the Investigator might impair the subject's tolerance or ability to participate in the trial.

Known severe hypersensitivity reactions to monoclonal antibodies.

Subject is pregnant or breast feeding or planning to become pregnant while enrolled in the study, up to the final (end of treatment) visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Standard Chemotherapy

Participants receive standard treatment with chemotherapy before placement of the PEDD catheter

4-6 weeks

Treatment with Nelitolimod

Participants receive 3 doses of Nelitolimod via TriNav PEDD catheter before undergoing liver resection

2-6 weeks

Liver Resection

Participants undergo liver resection surgery following treatment with Nelitolimod

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Nelitolimod

Trial Overview The INFINITIVE trial is testing Nelitolimod delivered directly to the liver using a special catheter called TriNav PEDD. The goal is to see if this treatment can activate the immune system against cancer without affecting the ability to safely perform liver surgery.

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07172282

NCT07172282 | INFINITIVE: ImmuNotherapy For PatIeNts ... To assess the safety of Nelitolimod delivered via PEDD in CRLM. To assess tumor regression score post-treatment with Nelitolimod and correlate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12536300/

Pressure enabled drug delivery (PEDD) of nelitolimod ... Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2622

PERIO-02: Phase 1b pressure enabled regional immuno- ... Results: At data cutoff, 29 pts [70% ICC, 30% HCC] were enrolled, 23 received at least one dose of nelitolimod: 3 in Cohort A (4 mg), 8 in ...

4. nature.com nature.com/articles/s41591-024-03250-w

Neoadjuvant nivolumab and relatlimab in locally advanced ... In our study, we observed an MPR rate of 92% in addition to a high pCR rate, both of which have been associated with an excellent outcome after ...

5. researchgate.net researchgate.net/publication/394718427_Phase_2_Open-Label_Multicenter_Study_of_Nelitolimod_in_Combination_with_Pembrolizumab_in_Anti-PD-1_Treatment-Naive_Advanced_Melanoma

Phase 2, Open-Label, Multicenter Study of Nelitolimod in ... Results Forty-five patients received nelitolimod 2 mg and 41 patients received nelitolimod 8 mg per injection. The objective response rate (ORR) ...

6. aacrjournals.org aacrjournals.org/clincancerres/article-abstract/31/19/4070/765503/Phase-2-Open-Label-Multicenter-Study-of

Phase 2, Open-Label, Multicenter Study of Nelitolimod in ... The objective response rate (ORR) was 76% in the 2-mg group and 49% in the 8-mg group. In those with distant metastases, ORRs in both treatment groups were ...

7. jitc.bmj.com jitc.bmj.com/content/12/7/e008837

Subcutaneous checkpoint inhibition is equivalent to ... The addition of Sys or SQ α-PD-1 to PEDD of nelitolimod further improved survival significantly, with 44% (4/9) of Sys and 50% (4/8) of SQ mice ...