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

Trial Summary

What is the purpose of this trial?

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 in patients with advanced or metastatic solid tumors. ODC-IL2 is a conditionally activated IL-2 prodrug and will be administered as a single agent via intravenous infusion on Days 1 and 15 of a 28-day cycle. Up to approximately 50 patients will be enrolled in this study.

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.

What data supports the effectiveness of the drug ODC-IL2 for cancer?

Research on interleukin-2 (IL-2), a component of ODC-IL2, shows that it can lead to long-term survival in a small number of patients with certain cancers like metastatic melanoma and renal cell carcinoma. Although IL-2 can have significant side effects, it has shown potential for durable responses in some patients. ^{1 2 3 4 5}

What safety data exists for ODC-IL2 or similar treatments in humans?

Interleukin-2 (IL-2) treatments, used for cancer, have shown significant side effects, including nausea, vomiting, fever, and fatigue, with severe cases affecting the lungs and heart. Low-dose IL-2 has been better tolerated, causing mild skin reactions and general side effects, while a modified version of IL-2 has shown lower toxicity in animal studies. ^{6 7 8 9 10}

What makes the drug ODC-IL2 unique for cancer treatment?

ODC-IL2 is unique because it involves the use of interleukin-2 (IL-2), which is known for its ability to activate immune cells like natural killer (NK) cells and T-cells to fight cancer. Unlike traditional chemotherapy, which targets cancer cells directly, IL-2 works by boosting the body's immune response, potentially leading to durable responses in some patients. ^{2 7 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Long-term survival after continuous infusion interleukin-2. [2004]

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

Clinical applications of IL-2. [2007]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

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

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

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

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

Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2. [2021]

6. England 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. [2018]

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

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

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

Daily subcutaneous injection of low-dose interleukin 2 expands natural killer cells in vivo without significant toxicity. [2020]

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

Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. [2020]

10. United States 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. [2019]

11. Czech Republic pubmed.ncbi.nlm.nih.gov

Interleukin-2 therapy of cancer. [2022]

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

Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity. [2019]

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

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