NHS-IL12 + M7824 for Kaposi Sarcoma

Overseen By Ramya M Ramaswami, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: ART

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Severe KS, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 32

Duration: 96 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Kaposi sarcoma (KS) tumors grow on the skin, lymph nodes, lungs, bone, and gastrointestinal tract. KS often affects people with immune deficiencies, such as among people living with HIV or those with prior history of transplant. Researchers want to see if 2 non-chemotherapy drugs can help people with KS. NHS-IL12 triggers the immune system to fight tumors. M7824 blocks the pathways that cancer cells use to stop the immune system from fighting tumors. Objective: To learn if giving NHS-IL12 alone or with M7824 could help the immune system fight KS tumors. Eligibility: People 18 and older with KS that has been treated with chemotherapy or immunotherapy Design: Participants will be screened with some or all of the following: medical history physical exam chest X-ray computed tomography scan blood and urine tests electrocardiogram and echocardiogram skin KS lesion biopsy lung exam gastrointestinal exam All participants will get NHS-IL12 every 4 weeks for up to 96 weeks (or 24cycles). It is injected under the skin. Some participants will also get M7824 every 2 weeks for up to 96 weeks (or 24cycles). It is given through a plastic tube that is put in an arm vein. Participants will complete questionnaires about how KS affects their quality of life. Their KS lesions will be measured and photographed. They will repeat some of the screening tests. They will give saliva samples or additional tissue samples. They will have a lung function test. Their ability to perform their normal activities will be assessed. The treatment duration is up to 96 weeks (or 24cycles) with an option to take NHS-IL12 and/or M7824 until the KS tumors are not responding, or you develop unacceptable side effects. Participants will have follow-up visits 7 and 30 days after treatment ends, then every 3 to 6 months for the next 18 months, then once a year for 3 years.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of 2 weeks from the last chemotherapy and 4 weeks from the last immunotherapy or other systemic treatments before starting the study. This means you may need to stop some current medications before participating.

What data supports the effectiveness of the drug NHS-IL12 + M7824 for Kaposi Sarcoma?

Research shows that interleukin-12 (IL-12), a component of the treatment, has shown promising results in treating AIDS-related Kaposi's sarcoma, with a significant number of patients experiencing partial or complete responses. This suggests that IL-12 may be effective in managing this condition. ^{1 2 3 4 5}

Is the treatment NHS-IL12 + M7824 generally safe for humans?

Interleukin-12 (IL-12), a component of the treatment, has been tested in humans with AIDS-related Kaposi sarcoma and was generally well tolerated, with some side effects like flu-like symptoms, changes in liver enzymes, low white blood cell counts, anemia, and depression. These studies suggest that IL-12 has acceptable safety in humans, but specific safety data for the combination with M7824 (Bintrafusp alfa) is not provided in the available research. ^{1 2 3 4 5}

What makes the drug NHS-IL12 unique for treating Kaposi Sarcoma?

NHS-IL12 is unique because it uses interleukin-12 (IL-12), a protein that boosts the immune system and has shown promise in treating Kaposi Sarcoma by enhancing immune responses and reducing blood vessel growth in tumors. This approach is different from standard treatments, as it specifically targets the immune system to fight the cancer. ^{1 2 3 4 6}

Research Team

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with Kaposi Sarcoma (KS) who've had prior treatments that didn't work well can join. This includes those living with HIV, provided they meet certain viral load and immune cell count criteria. Participants need measurable KS lesions and good organ/marrow function. They must not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

You have a specific type of measurable disease according to the AIDS Clinical Trials Group (ACTG) Oncology Committee criteria for KS.

My organs and bone marrow are functioning well.

I have not had chemotherapy in the last 2 weeks or immunotherapy in the last 4 weeks.

Exclusion Criteria

I do not have any untreated serious infections.

I have been diagnosed with active multicentric Castleman disease.

I have had cancer other than Kaposi's sarcoma, but under certain conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive NHS-IL12 every 4 weeks for up to 96 weeks, with some also receiving M7824 every 2 weeks

96 weeks

24 visits (in-person) for NHS-IL12, 48 visits (in-person) for M7824

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up visits 7 and 30 days after treatment ends, then every 3 to 6 months for 18 months, then annually

Treatment Details

Interventions

• M7824
• NHS-IL12

Trial Overview The trial is testing NHS-IL12 alone or combined with M7824 in treating KS. NHS-IL12 boosts the immune system against tumors, while M7824 blocks cancer pathways that inhibit the immune response. The drugs are given via injections under the skin or through a vein for up to 96 weeks.

Participant Groups

Group I: Arm 2/Combination therapy Experimental Treatment 2 Interventions

Treatment with NHS-IL12 at MTD and M7824 at a fixed dose

Group II: Arm 1a/Monotherapy Expansion Experimental Treatment 1 Intervention

Treatment with NHS-IL12 at MTD

Group III: Arm 1/Monotherapy Experimental Treatment 1 Intervention

Treatment with NHS-IL12 at de-escalating doses if necessary

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Interleukin-12 (IL-12) shows promise as a potential treatment for Kaposi's sarcoma (KS), particularly in patients with AIDS-associated KS, as indicated by a phase I pilot study that demonstrated anti-KS activity when used alone.

In combination with liposomal doxorubicin and antiretroviral therapy, IL-12 led to significant remissions in a substantial percentage of patients with advanced AIDS-associated KS, suggesting its efficacy in enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of AIDS-related Kaposi's sarcoma with interleukin-12: rationale and preliminary evidence of clinical activity. Yarchoan, R., Pluda, JM., Wyvill, KM., et al.[2019]

In a phase 1 pilot study involving 32 patients with AIDS-related Kaposi sarcoma, IL-12 treatment showed a significant response rate of 71% at higher doses (500 ng/kg), indicating its potential efficacy against this cancer.

The treatment was generally well-tolerated, with manageable side effects like flu-like symptoms and blood count changes, suggesting that IL-12 could be a promising option for patients whose disease is progressing despite antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Little, RF., Pluda, JM., Wyvill, KM., et al.[2021]

In a study involving four patients with epidemic Kaposi's sarcoma (EKS), treatment with recombinant interleukin-2 (IL-2) and interferon-beta did not yield any objective responses, and three patients experienced rapid disease progression shortly after starting therapy.

The findings suggest that high doses of IL-2 may lead to increased levels of gamma-interferon, which could negatively impact treatment outcomes, indicating a need for careful monitoring of IFN-gamma levels in future IL-2 therapies for EKS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exacerbation of epidemic Kaposi's sarcoma with a combination of interleukin-2 and beta-interferon: results of a phase 2 study. Krigel, RL., Padavic-Shaller, KA., Rudolph, AR., et al.[2015]

In a study of 36 patients with AIDS-associated Kaposi sarcoma, the combination of pegylated liposomal doxorubicin and interleukin-12 resulted in an impressive 83.3% major response rate, including 9 complete responses, demonstrating the efficacy of this treatment regimen.

The treatment was well tolerated overall, with manageable side effects such as neutropenia and anemia, and showed sustained responses during maintenance therapy with IL-12, suggesting its potential for long-term effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. Little, RF., Aleman, K., Kumar, P., et al.[2021]

In a study of 18 patients with AIDS-related Kaposi's sarcoma, subcutaneous administration of interleukin-4 (IL-4) resulted in significant hematologic adverse effects, particularly grade 4 neutropenia in 33% of patients, indicating potential safety concerns.

Despite minimal anti-tumor effects overall, some patients experienced a decrease in plasma HIV RNA levels after four weeks of IL-4 therapy, suggesting a possible immunologic benefit, especially in patients with better immune status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-4 in the treatment of AIDS-related Kaposi's sarcoma. Tulpule, A., Joshi, B., DeGuzman, N., et al.[2020]

Lentiviral transduction of human sarcoma cells to produce interleukin-12 (IL-12) allows for localized delivery of this cytokine, enhancing both innate and adaptive immune responses without the systemic toxicities associated with traditional IL-12 administration.

In murine models, IL-12 expressing sarcomas not only restricted tumor growth but also triggered a specific immune response, indicating that this method could be a promising approach for treating sarcomas through autologous reintroduction of modified tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarcoma IL-12 overexpression facilitates NK cell immunomodulation. Rademacher, MJ., Cruz, A., Faber, M., et al.[2021]

References

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

Treatment of AIDS-related Kaposi's sarcoma with interleukin-12: rationale and preliminary evidence of clinical activity. [2019]

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

Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. [2021]

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

Exacerbation of epidemic Kaposi's sarcoma with a combination of interleukin-2 and beta-interferon: results of a phase 2 study. [2015]

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

Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. [2021]

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

Interleukin-4 in the treatment of AIDS-related Kaposi's sarcoma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Sarcoma IL-12 overexpression facilitates NK cell immunomodulation. [2021]