Immunotherapy with TLR Agonist for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals, Immunosuppressants, Corticosteroids, others

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 30

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of MGN1703, an experimental drug, when combined with ipilimumab (Yervoy), a medication used to treat certain cancers. The trial focuses on patients with advanced tumors that have not responded to other treatments. Researchers will also assess the safety of this combination for participants. Suitable candidates for this trial have advanced cancer that hasn't improved with standard treatments and have recently undergone radiation. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

Participants must stop taking prior chemotherapy, hormonal therapy, or biological therapy for at least 4 weeks before joining the trial, except for prostate cancer patients who can continue LHRH agonist treatment. The protocol does not specify other medications, so it's best to discuss with the study team.

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

Research has shown that MGN1703, when used alone, was generally well tolerated, with most side effects being mild. Studies have found MGN1703 to have a good safety profile. Researchers are now studying the safety of using MGN1703 with ipilimumab, a drug already approved for some cancers, in different administration methods.

In previous studies, participants who took MGN1703 reported mild side effects, consistent with earlier findings. Ipilimumab, the other drug in this study, is already safely used in patients with certain advanced cancers. The current focus is on determining the best dose when both drugs are used together.

This study is in its early stages, so researchers are still determining the safest dose levels. Early-phase studies like this one focus on safety, and the results will help ensure that any side effects remain minimal and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of MGN1703 and Ipilimumab for cancer treatment because it offers a novel approach compared to the standard options like chemotherapy and radiation. Most conventional treatments work by directly killing cancer cells, but MGN1703 is a TLR agonist that boosts the body's immune response to target cancer cells more effectively. Additionally, the combination includes Ipilimumab, an immunotherapy that further enhances the immune system's ability to fight cancer by blocking a protein that inhibits immune activity. This dual approach of activating and unleashing the immune response is promising because it may lead to more effective and longer-lasting cancer control.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that ipilimumab, a treatment approved by the FDA, effectively treats advanced melanoma by helping the immune system find and attack cancer cells. MGN1703 is a new drug that activates immune cells, but it has not yet received approval. In this trial, participants will receive a combination of MGN1703 and ipilimumab. Early research suggests that MGN1703 might strengthen the immune response against tumors. Some studies indicate that combining MGN1703 with ipilimumab could enhance the treatment's effectiveness for advanced cancers. This combination aims to boost the body's ability to fight cancer more than ipilimumab alone. ^{3 6 7 8 9}

Who Is on the Research Team?

David Hong, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that standard therapy has failed to cure or for which no standard treatment exists can join this trial. They must have been off other treatments for at least 4 weeks, have a stable health status, and agree to use contraception. People with severe allergies to the study drugs, recent vaccines, certain infections or diseases like severe autoimmune disorders cannot participate.

Inclusion Criteria

Patients must be willing and able to review, understand, and provide written consent before study enrollment

You have a disease that can be measured using specific criteria.

My cancer is advanced or has spread, and standard treatments haven't worked or aren't available.

Exclusion Criteria

I have not had radiation therapy in the last 4 weeks.

I have had serious gut issues like diverticulitis or blockages.

I don't have any health issues that could make the study drug dangerous for me or affect the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MGN1703 and ipilimumab over 4 cycles, each cycle lasting 21 days. MGN1703 is administered subcutaneously on Days 1, 8, and 15, and ipilimumab is administered intravenously on Day 8 of each cycle.

12 weeks

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes phone calls every 30 days for 90 days after the last dose to check on new anticancer drugs and overall health.

12 weeks

Phone calls every 30 days

Extension

Participants may continue receiving MGN1703 alone if deemed beneficial by the doctor, until disease progression or intolerable side effects occur.

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• MGN1703

Trial Overview The trial is testing the highest dose of MGN1703 (not FDA approved) that's safe when given with ipilimumab (FDA approved for melanoma) in patients with advanced tumors. Researchers want to see how well these two drugs work together and what side effects they might cause.

How Is the Trial Designed?

Group I: MTD Post XRT Group: MGN1703 (subcutaneously) + Ipilimumab Experimental Treatment 2 Interventions

Dose expansion group consists of participants with advanced malignancy treated with radiation (XRT) within the past 2 weeks. MGN1703 given subcutaneously at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.

Group II: MTD Group: MGN1703 (subcutaneously) + Ipilimumab Experimental Treatment 2 Interventions

Dose expansion group consists of participants with advanced malignancy and cutaneous or subcutaneous manifestations. MGN1703 given subcutaneously at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.

Group III: MTD Group: MGN1703 (intratumoral injection) + Ipilimumab Experimental Treatment 2 Interventions

Dose expansion group consists of participants with advanced malignancy and cutaneous or or subcutaneous manifestations. MGN1703 given by intratumoral injection at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.

Group IV: Dose Escalation Group: MGN1703 + Ipilimumab Experimental Treatment 2 Interventions

Participants receive MGN1703 on Days 1, 8, and 15 of all cycles as an injection under the skin. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long. Participants receive a total of 4 treatment cycles for a total of 12 weeks on treatment.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Mologen AG

Industry Sponsor

Trials

7

Recruited

770+

Published Research Related to This Trial

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Ipilimumab, an antibody that enhances T-cell activation, is effective for treating metastatic melanoma but can cause immune-mediated side effects, including rare cases of ileitis without colitis, as seen in a 54-year-old patient.

The study highlights the need for further research into genetic and epigenetic factors to personalize treatment and minimize adverse effects associated with ipilimumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. Venditti, O., De Lisi, D., Caricato, M., et al.[2018]

Ipilimumab is a monoclonal antibody that blocks CTLA-4, enhancing T-cell activation and leading to significant antitumor immune responses, which has been shown to improve survival in patients with advanced melanoma in two global phase 3 clinical studies involving over 13,000 patients.

Approved in over 40 countries, including the U.S. and EU, ipilimumab is the first treatment to demonstrate an overall survival benefit for advanced melanoma, with ongoing trials exploring its efficacy in other cancers like lung and gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ipilimumab]. Tokudome, T.[2017]

In a review of 129 oncology patients treated with immune checkpoint inhibitors, 51.9% experienced at least one immune-related adverse event (irAE), highlighting the common occurrence of these side effects.

Nearly half of the irAEs were managed according to established guidelines, but there was significant variability in documentation and management practices, indicating a need for improved adherence as immunotherapy use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. Teimouri, A., Minard, LV., Scott, SN., et al.[2022]

Ipilimumab, an anti-CTLA-4 antibody, has been shown to improve survival in patients with unresectable or metastatic melanoma, with a standard dosing of 3 mg/kg every 3 weeks for a total of 4 doses.

While ipilimumab can cause immune-related adverse events in 15% of patients, most are mild and manageable; however, high-grade events can be serious and require careful monitoring and treatment with corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a pharmacologic perspective. Trinh, VA., Hagen, B.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02668770?cond=Cancer&aggFilters=funderType%3Aindustry%2CstudyType%3Aint

Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist ... The goal of this clinical research study is to find the highest tolerable dose of MGN1703 that can be given in combination with ipilimumab to patients with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2564

Lefitolimod (TLR agonist) and ipilimumab in patients with ... This trial assessed the safety and preliminary efficacy of the rational combination of lefitolimod with ipilimumab in patients (pts) with advanced solid tumors.

3. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/nct02668770/

Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist ... Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies. Program Status. Clinical trial's patient recruitment status.

4. clinicaltrial.be clinicaltrial.be/en/details/10503?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist ... You will be given MGN1703 as an injection under the skin on Days 1, 8, and 15 of each cycle. Each administration will be between 1-4 injections ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11824599/

Lefitolimod in Combination with Ipilimumab in Patients ... TLR9 agonists, such as lefitolimod (MGN1703), significantly increased Th1 response in preclinical models and have demonstrated efficacy in early clinical trials ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02668770

Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist ... The goal of this clinical research study is to find the highest tolerable dose of MGN1703 that can be given in combination with ipilimumab to patients with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4131138/

Maintenance treatment with the immunomodulator MGN1703 ... Safety data for MGN1703 were in accordance with those from the phase I trial (Weihrauch et al., submitted). MGN1703 was generally well tolerated, with most ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT71348

Preliminary results of an ongoing phase II/III clinical study ... The antineoplastic activity of MGN1703 was previously shown in several in-vitro and in-vivo models. A good safety profile of MGN1703 was shown in regulatory ...

9. meridian.allenpress.com meridian.allenpress.com/innovationsjournals-JIPO/article/8/2/89/505520/Lefitolimod-in-Combination-with-Ipilimumab-in

Lefitolimod in Combination with Ipilimumab in Patients ... This trial assessed the safety and preliminary efficacy of the combination of lefitolimod and ipilimumab in patients with advanced solid tumors.