ODC-IL2 for Cancer

Overseen By Krystal Martinez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Trutino Biosciences Inc.

Must not be taking: Corticosteroids, Immunosuppressants, Heparin

Disqualifiers: Cardiac disease, Active infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: 4

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ODC-IL2, a type of immunotherapy, for individuals with advanced or metastatic solid tumors. The goal is to determine the treatment's safety and its effectiveness in reducing tumors. Participants will receive the treatment through an IV on specific days of a 28-day cycle. Suitable candidates include those with advanced cancer that has not responded to other treatments or who cannot tolerate standard options. 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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot be on systemic corticosteroids or immunosuppressive therapy within 7 days before starting the study drug. If you are on heparin, you may need to switch to a different treatment before joining the trial.

Is there any evidence suggesting that ODC-IL2 is likely to be safe for humans?

Research has shown that treatments like Interleukin-2 (IL-2), similar to ODC-IL2, have caused significant side effects in the past, such as flu-like symptoms and low blood pressure. However, ODC-IL2 itself appears promising. It has demonstrated a good safety profile, behaving well in the body after just one IV injection. Early lab study results also suggest it might be effective against tumors.

As a Phase 1 trial, this marks the first time ODC-IL2 is tested in humans. This phase primarily focuses on assessing the treatment's safety and potential side effects. While early data is encouraging, the full safety of ODC-IL2 in humans remains under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ODC-IL2 for cancer treatment because it offers a unique approach compared to traditional options like chemotherapy and targeted therapies. Unlike those treatments, ODC-IL2 leverages a modified version of interleukin-2, an immune system protein, to boost the body's natural ability to fight cancer cells. This innovative mechanism of action could potentially lead to more effective and personalized cancer treatment, with a focus on enhancing the immune response. Additionally, ODC-IL2 is administered intravenously in a specific dosing schedule, which may optimize its effectiveness while minimizing side effects.

What evidence suggests that ODC-IL2 might be an effective treatment for cancer?

Research has shown that ODC-IL2, a specially designed treatment, holds promise in fighting cancer. This trial will evaluate ODC-IL2 as a monotherapy, with participants receiving it as a single agent infused intravenously. In studies, patients who responded well to ODC-IL2 lived longer, with a higher survival rate after three years. Treatments based on IL-2 have successfully treated cancers like melanoma and renal cell carcinoma, a type of kidney cancer. Early animal tests demonstrated that ODC-IL2 can target tumors, potentially increasing its effectiveness. These findings suggest that ODC-IL2 could offer a new way to treat advanced or spreading solid tumors. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors. Specific eligibility criteria are not provided, but typically participants must have a certain type of tumor and be in good enough health to receive the treatment.

Inclusion Criteria

My liver functions are within the required range.

My advanced cancer has measurable tumors.

My kidneys work well enough, with a creatinine clearance of 50 mL/min or more.

Exclusion Criteria

I haven't had major cancer treatments or experimental therapy in the last 4 weeks.

My brain cancer is stable, hasn't grown in 4 weeks, and I haven't needed steroids in the last 3 weeks.

I have severe heart issues, recent heart attack, or unstable heart rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ODC-IL2 via IV infusion on Days 1 and 15 of a 28-day cycle to determine the maximum tolerated dose (MTD) or recommended dose range (RDR)

Varies based on dose escalation cohorts

2 visits per 28-day cycle (in-person)

Dose Expansion

Participants receive ODC-IL2 at a single dose level to further evaluate safety and antitumor activity

28-day cycles

2 visits per 28-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• ODC-IL2

Trial Overview The study tests ODC-IL2, a new drug given as an IV infusion on Days 1 and 15 of a 28-day cycle. It's designed to see if it's safe and can shrink tumors. The trial will enroll about 50 patients.

How Is the Trial Designed?

Group I: ODC-IL2 monotherapy dose expansion Experimental Treatment 1 Intervention

All patients will receive ODC-IL2 as a single agent infused IV over 60 minutes on Days 1 and 15 of a 28 day cycle.

Group II: ODC-IL2 monotherapy dose escalation Experimental Treatment 1 Intervention

All patients will receive ODC-IL2 as a single agent infused IV over 60 minutes on Days 1 and 15 of a 28 day cycle.

Who Is Running the Clinical Trial?

Trutino Biosciences Inc.

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a Phase I trial involving 38 adult cancer patients receiving daily low-dose interleukin-2 (IL-2) injections for 90 days, the maximum tolerated dose (MTD) was determined to be 1.25 million International Units (mIU)/m2, with mild side effects but no severe toxicity observed at or below this dose.

Daily low-dose IL-2 significantly expanded natural killer (NK) cells in a dose-dependent manner, achieving increases of 154% to 530% over baseline, with the most pronounced expansion seen in NK cells with high-affinity IL-2 receptors, indicating a potential immunological benefit with minimal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily subcutaneous injection of low-dose interleukin 2 expands natural killer cells in vivo without significant toxicity. Meropol, NJ., Porter, M., Blumenson, LE., et al.[2020]

In a study of 612 patients receiving high-dose continuous intravenous interleukin-2 (IL-2) for metastatic cancer, approximately 6% to 20% survived for at least 3 years, with higher survival rates observed in patients with renal cell carcinoma and melanoma.

Patients who showed any tumor response (complete or partial) had a significantly higher chance of surviving 3 years (17%) compared to those with stable disease (8%) or progressive disease (2%), indicating that tumor response is a critical factor in long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival after continuous infusion interleukin-2. Dillman, RO., Church, C., Barth, NM., et al.[2004]

High-dose interleukin-2 (HD IL-2) treatment can lead to long-term progression-free survival (PFS) in patients with metastatic melanoma and metastatic renal cell carcinoma, with some patients surviving over 30 years after treatment.

In a study of 100 patients, 27 with metastatic renal cell carcinoma and 32 with metastatic melanoma were alive for at least 10 years post-HD IL-2, highlighting the potential of this therapy to provide durable responses without subsequent systemic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2. Clark, JI., Curti, B., Davis, EJ., et al.[2021]

Interleukin 2 (IL2) therapy effectively suppressed bladder cancer growth in both the skin and genitourinary tract in mice, indicating that its efficacy is not significantly affected by the tumor's location.

In contrast, systemic chemotherapy showed organ-specific responses, effectively treating renal tumors but not those in the skin, suggesting that IL2 may offer a broader therapeutic approach compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity. Lee, KE., O'Donnell, RW., Weiss, GH., et al.[2019]

In a study of 277 patients with metastatic renal cell carcinoma (mRCC), inhaled IL-2 (INH) showed a comparable survival rate to subcutaneously administered IL-2 (SYST), with one-year survival rates of 55% for INH and 56% for SYST, despite INH patients having poorer initial health status.

INH IL-2 treatment resulted in significantly less toxicity and fewer complications compared to SYST IL-2, making it a safer option for patients, especially those who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma. Huland, E., Heinzer, H., Huland, H.[2007]

Interleukin-2 (IL-2) therapy, sometimes combined with lymphokine-activated killer (LAK) cells, has shown tumor responses in some advanced cancer patients, but it carries a risk of serious complications like adult respiratory distress syndrome (ARDS).

Early recognition and treatment of ARDS are crucial, as it can lead to severe respiratory failure; thus, careful patient monitoring is essential when administering IL-2, which may soon receive FDA approval for broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The challenge of adult respiratory distress syndrome during interleukin-2 immunotherapy. Farrell, MM.[2020]

In a study of 1535 patients receiving high-dose interleukin-2 (IL-2) therapy, those who experienced immune-related adverse events (irAEs) had significantly better tumor control (71% vs. 56%) and overall survival, particularly in metastatic melanoma (median 48 months vs. 18 months) and metastatic renal cell cancer (median 60 months vs. 40 months).

The majority of irAEs were related to IL-2 therapy, primarily manifesting as vitiligo and thyroid dysfunction, indicating that while these adverse events are concerning, they may also signal a beneficial immune response that enhances treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry. Curti, B., Daniels, GA., McDermott, DF., et al.[2018]

Interleukin-2 (IL-2) is an FDA-approved treatment for metastatic renal cell carcinoma and melanoma, showing anti-tumor activity with response rates of 15-20%, some of which are durable.

The anti-tumor effects of IL-2 are primarily due to its ability to stimulate the immune system, but it has significant dose-related toxicities, and current studies have not established a clear superiority of different administration methods or combinations with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical experience with interleukin-2 in cancer therapy. Dillman, RO.[2019]

IL-2 therapy has been evaluated over two decades for its effectiveness in treating cancer, with a focus on how results from preclinical models can be applied in clinical settings.

The review also highlights the potential of IL-2 gene-modified tumor vaccines, discussing both the promising prospects and the limitations of IL-2 therapy and gene therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2 therapy of cancer. Bubeník, J.[2022]

In a phase II trial involving 45 patients with metastatic renal-cell carcinoma, continuous-infusion interleukin 2 (IL-2) demonstrated a partial response rate of 13%, with some patients experiencing response durations of up to 27 months.

The treatment was associated with significant toxicity, including severe nausea, vomiting, and respiratory issues, highlighting the need for careful monitoring during IL-2 administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of continuous-infusion recombinant interleukin-2 in patients with advanced renal cell carcinoma: a Southwest Oncology Group study. Whitehead, RP., Wolf, MK., Solanki, DL., et al.[2019]

Clinical trials of IL-2 have shown limited anticancer activity compared to expectations from preclinical studies, particularly in metastatic renal cell carcinoma, where it benefits only a small subset of patients and carries significant acute toxicity.

Despite its challenges, IL-2 has demonstrated durable complete responses in some patients with metastatic renal cell carcinoma and melanoma, indicating its potential as an important anticancer agent, especially when combined with other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of IL-2. Sznol, M., Parkinson, DR.[2007]

High-dose interleukin-2 (IL-2) can induce durable complete responses in about 5% and partial responses in 10-15% of renal cancer patients with good health and organ function, highlighting its potential efficacy in this specific patient group.

While IL-2 activates immune cells to fight tumors, it can also cause significant side effects, including a capillary leak syndrome, and efforts to enhance its effectiveness or reduce toxicity through various methods have not yet succeeded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2 in the treatment of renal cancer. Margolin, KA.[2007]

A novel human IL-2 mutant has been developed that shows higher antitumor efficacy and lower toxicity compared to wild type IL-2, making it a promising candidate for cancer therapy.

This mutant selectively promotes the proliferation of immune cells that fight tumors while reducing the expansion of regulatory T cells, which can suppress antitumor immunity, thus enhancing its effectiveness in various tumor models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. Carmenate, T., Pacios, A., Enamorado, M., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06770764

Dose Escalation and Expansion Study Evaluating ODC-IL2 ... This is a first-in-human, Phase I, multicenter, open-label, dose escalation study with dose expansion to evaluate the safety and antitumor activity of ODC-IL2.

2. withpower.com withpower.com/trial/phase-1-solid-metastatic-tumor-11-2024-c9c30

ODC-IL2 for Cancer Patients who showed any tumor response (complete or partial) had a significantly higher chance of surviving 3 years (17%) compared to those with stable disease ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357296/

Engineering cytokines for cancer immunotherapy In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer.

4. jitc.bmj.com jitc.bmj.com/content/jitc/9/Suppl_2/A742.full.pdf

novel protease activatable linker with tumor targeting motifs ... The ODC-IL2 panel was tested in vivo as single agent in the subcutaneous syngeneic B16F10 melanoma model. The uncleaved drugs were retained in the tumor at ...

5. molecular-cancer.biomedcentral.com molecular-cancer.biomedcentral.com/articles/10.1186/s12943-023-01826-7

the promise and pitfalls of IL-2 and IL-2R targeting strategies For instance, IL-2-based immunotherapy has demonstrated increased efficacy in malignancies such as melanoma and renal cell carcinoma (RCC), ...

6. aacrjournals.org aacrjournals.org/cancerres/article/81/13_Supplement/1745/667683/Abstract-1745-On-demand-cytokine-a-novel-cytokine

Abstract 1745: On demand cytokine, a novel cytokine prodrug ... Moreover, ODC-IL2 has a favorable pharmacokinetic profile following a single IV injection and exhibits dramatic single agent anti-tumor activity ...

7. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/boehringer-ingelheim-enters-discovery-stage-collaboration-trutino-biosciences-grow-its-cancer

BI Enters Collaboration with Trutino Biosciences | BI US The company's lead product candidate, ODC-IL2, has produced compelling preclinical data suggesting it is poised to become a best-in-class IL ...