Immunotherapy + Radiation for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Auto-immune disease, Brain metastases, Hepatitis, others

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

Compensation: Varies

Number of Visits: 7

Duration: 1 week

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for certain cancers that cannot be surgically removed or have spread. It combines a special protein treatment, M5A-IL2 immunocytokine (M5A-ICK), with targeted radiation therapy to evaluate their combined effectiveness. The trial aims to determine the optimal dose and monitor for side effects. It targets individuals with colorectal or breast cancer that produces a specific protein (CEA) and who have not responded to standard treatments. Participants should have up to five cancer spots treatable with radiation. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 4 weeks from your last cytotoxic or biological agent, except for mitomycin C, which requires a 6-week break, and prior immunotherapy, which requires a 3-month break before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the M5A-IL2 immunocytokine (M5A-ICK) may help target cancer cells and boost the immune system. Previous studies have explored its effects when combined with radiation, similar to what this trial tests. Although specific safety data for M5A-ICK in humans remains limited, similar treatments have been well-tolerated. For example, a related treatment, F16-IL-2, was safe when used with chemotherapy for breast cancer.

Stereotactic Body Radiation Therapy (SBRT), part of this treatment, has a well-known safety record. Studies have shown that SBRT can precisely target tumors, leading to fewer side effects than traditional radiation methods. Most patients handle it well, with only a few experiencing severe side effects.

As this is an early-phase trial, the main goal is to identify any side effects and determine the best dose of M5A-ICK with SBRT. The treatment is still being tested for safety in humans, so participants will be closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cancer rely on chemotherapy or traditional radiation, which can affect both cancerous and healthy cells. But the M5A-IL2 immunocytokine (M5A-ICK) is unique because it combines immunotherapy with a targeted cytokine approach. This means it aims to stimulate the body's immune system specifically to attack cancer cells without harming normal cells. Researchers are excited about this treatment because it has the potential to enhance the precision and effectiveness of radiation therapy, potentially leading to better outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for colorectal cancer or CEA positive breast cancer?

In this trial, participants will receive a combination of Stereotactic Body Radiation Therapy (SBRT) and the M5A-IL2 immunocytokine (M5A-ICK). Research has shown that the M5A-IL2 immunocytokine can effectively target and shrink tumors. M5A-ICK combines an anti-cancer antibody with a protein that enhances the immune system's ability to fight cancer, focusing its effects on cancer cells that produce a specific marker called carcinoembryonic antigen (CEA). Previous studies have demonstrated that these immunocytokines can lead to better tumor shrinkage and improved survival rates.

Stereotactic Body Radiation Therapy (SBRT) is also highly effective, with some studies indicating it can control tumors in 80% to 90% of certain cancer cases. Combining these treatments in this trial may improve overall effectiveness, particularly for cancers that are difficult to remove or have spread. ^{1 2 3 6 7}

Who Is on the Research Team?

Jeffrey Wong

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal or CEA positive breast cancer that's not operable. Participants must have stable health, an expected survival of at least 3 months, and meet specific blood count and organ function criteria. They should be past certain waiting periods after previous treatments and agree to use effective contraception if applicable.

Inclusion Criteria

Your liver enzymes (AST/ALT) should be within a certain range.

Your platelet count is higher than 100,000 per cubic millimeter.

Your bilirubin levels are within the normal range.

Exclusion Criteria

My electrolyte levels cannot be corrected to a mild condition.

I have active cancer spread to my brain.

I am of child-bearing age and do not use birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation

Participants undergo standard of care SBRT over 3 fractions on days 1, 3, and 5

1 week

3 visits (in-person)

Treatment

Participants receive M5A-IL2 immunocytokine subcutaneously on days 8, 9, and 10

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• M5A-IL2 immunocytokine (M5A-ICK)
• Stereotactic Body Radiation Therapy

Trial Overview The trial tests M5A-IL2 immunocytokine combined with stereotactic body radiation therapy (SBRT) to treat unresectable metastatic cancers. It aims to find the safest dose and see how well it works by targeting cancer cells while activating the immune system.

How Is the Trial Designed?

Group I: Treatment (SBRT, M5A-IL2 ICK) Experimental Treatment 8 Interventions

Patients undergo SOC SBRT over 3 fractions on days 1, 3, and 5, followed by M5A-ICK SC on days 8, 9, and 10 once daily for a single cycle on study. Patients undergo CT or PET/CT as well as blood sample collection throughout the trial. Patients may undergo magnetic resonance imaging or bone scan as clinically indicated on the trial. Additionally, patients may optionally undergo tissue biopsy during screening and on study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Combining local radiotherapy with intratumoral injections of tumor-specific antibodies, particularly an IL2-linked immunocytokine, significantly enhances antitumor immune responses, leading to complete tumor regression in most tested mice with melanoma, neuroblastoma, and head and neck squamous cell carcinoma.

The addition of immune checkpoint blockade to this combination therapy further improves tumor response and survival in mice with large tumors or metastases, suggesting a promising strategy for enhancing cancer treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Situ Tumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments. Morris, ZS., Guy, EI., Francis, DM., et al.[2018]

The antibody-IL-2 fusion protein (ICK) targeting CEA-positive tumors showed significant tumor eradication in a transgenic mouse model, indicating its potential as an effective cancer treatment.

ICK therapy reduced the presence of regulatory T cells (Tregs) in tumors compared to anti-CEA antibody treatment, suggesting it may enhance anti-tumor immunity without increasing Treg activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation. Kujawski, M., Sherman, M., Hui, S., et al.[2021]

IL-2 immunocytokines effectively target the tumor microenvironment, promoting the activation of natural killer (NK) cells and cytotoxic CD8+ T lymphocytes, which helps shift the immune response towards a more effective anti-tumor response.

These immunocytokines can achieve potent anti-cancer effects while minimizing severe toxicities associated with high-dose systemic IL-2, as shown in preclinical models and early clinical trials, and they show promise when combined with other cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy. Mortara, L., Balza, E., Bruno, A., et al.[2020]

In a phase 1 clinical trial involving 6 patients with oligometastatic solid tumors, the immunocytokine L19-IL2 was found to be well tolerated at a dose of 15 million International Units (Mio IU) after stereotactic body radiation therapy (SBRT), with no dose-limiting toxicity reported.

The study identified 2 long-term progression-free responders, suggesting potential therapeutic efficacy, and established that the recommended phase 2 dose for future trials combining SBRT with L19-IL2 is 15 Mio IU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of L19-Interleukin 2 Combined with Stereotactic Body Radiation Therapy: A Phase 1 Study. Van Limbergen, EJ., Hoeben, A., Lieverse, RIY., et al.[2021]

In a study involving 61 melanoma and neuroblastoma patients, 52% developed an anti-idiotypic antibody response to the immunocytokine hu14.18-IL2, which may interfere with the detection of the treatment in the bloodstream.

The development of these antibodies did not correlate with any clinical toxicity, suggesting that while the immune response occurs, it does not negatively impact patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma. Hank, JA., Gan, J., Ryu, H., et al.[2023]

Irradiation of rhabdomyosarcoma (A204) xenografts significantly increased the accumulation of the immunocytokine NHS-IL12, suggesting that combining radiation therapy with NHS-IL12 could enhance its anti-tumor effects.

In contrast, prostate cancer (PC3) xenografts did not show increased NHS-IL12 uptake after irradiation, indicating that the effectiveness of this treatment may depend on the specific type of tumor being targeted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced binding of necrosis-targeting immunocytokine NHS-IL12 after local tumour irradiation in murine xenograft models. Eckert, F., Schmitt, J., Zips, D., et al.[2021]

In preclinical studies, the combination of NHS-IL2 and radiotherapy led to significant tumor regression in 80%-100% of treated mice, indicating strong antitumor activity.

In a phase Ib trial with 13 patients suffering from metastatic non-small cell lung carcinoma, NHS-IL2 was well tolerated, with no maximum tolerated dose reached, and two patients experienced long-term survival, suggesting potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy. van den Heuvel, MM., Verheij, M., Boshuizen, R., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7028338/

Potent immunomodulatory effects of an anti-CEA-IL-2 ... While anti-CEA antibodies have no direct effect on CEA-positive tumors, they can be used to direct potent anti-tumor effects as an antibody-IL-2 fusion protein.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-07592

Immune Response Activation for the Treatment of ... This phase I trial studies the side effects and best dose of M5A-IL2 immunocytokine (M5A-ICK) combined with stereotactic body radiation therapy (SBRT)

3. jnm.snmjournals.org jnm.snmjournals.org/content/early/2022/06/30/jnumed.122.264126

Improved tumor responses with sequential targeted alpha ... Conclusion: Low dose (7.4 kBq) TAT followed by a 4 dose immunocytokine regimen 5 or 10 days later gave superior tumor reductions and survival ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071099/

Development and Potent Anti-Tumor Activity of a Fully ... Development and potent anti-tumor activity of a fully humanized anti-TAG-72-IL-2 fusion protein for therapy of solid tumors.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211383524003149

Advancements and challenges in immunocytokines The immunocytokine L19–IL2 eradicates cancer when used in combination with CTLA-4 blockade or with L19-TNF. J Invest Dermatol, 133 (2013), pp. 751-758. Google ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11357675/

Stimulating the Antitumor Immune Response Using ... F16-IL-2 showed beneficial signs and acceptable tolerability in combination with chemotherapy for the treatment of solid tumors and metastatic breast cancer [ ...

7. withpower.com withpower.com/trial/phase-1-carcinoma-2024-ff58b

Immunotherapy + Radiation for Cancer This phase I trial studies the side effects and best dose of M5A-IL2 immunocytokine (M5A-ICK) combined with stereotactic body radiation therapy (SBRT) and ...