NHS-IL12 + M7824 for Kaposi Sarcoma

Overseen By Irene B Ekwede, R.N.

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two non-chemotherapy drugs, NHS-IL12 and M7824 (Bintrafusp alfa), can help the immune system combat Kaposi Sarcoma (KS), a cancer often affecting individuals with weakened immune systems, such as those living with HIV. NHS-IL12 boosts the immune response against tumors, while M7824 blocks cancer's defenses against the immune system. People with KS previously treated with chemotherapy or immunotherapy but still requiring treatment may be suitable for this trial. Participants will receive NHS-IL12 injections, with some also receiving M7824, to evaluate the effectiveness of these treatments individually and together. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Research has shown that NHS-IL12 is usually well-tolerated by patients. In studies, this treatment has demonstrated promise in helping the body fight tumors, with no major safety issues reported.

For M7824, research indicates it can prevent cancer cells from hindering the immune system. Early findings suggest this treatment is safe and effective for patients with virus-related cancers, such as Kaposi sarcoma.

Both NHS-IL12 and M7824 remain under investigation. However, early studies indicate they are generally well-tolerated by patients. Participants should report any side effects experienced during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Kaposi Sarcoma, which often include chemotherapy or antiretroviral therapy, NHS-IL12 offers a new approach by targeting the immune system directly. NHS-IL12 is unique because it involves a cytokine fusion protein designed to enhance the body's immune response against cancer cells. In the combination therapy with M7824, NHS-IL12 is paired with a bifunctional protein that blocks certain pathways cancer cells use to evade the immune system. Researchers are excited about these treatments because they have the potential to offer a more targeted attack on cancer cells while potentially reducing the side effects associated with traditional therapies.

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

Research has shown that NHS-IL12, which participants in this trial may receive, can effectively activate the immune system to fight tumors. In early studies, patients with Kaposi sarcoma (KS) experienced a 50–71% positive response to treatments using similar immune-boosting drugs. M7824, another treatment option in this trial, helps prevent cancer cells from turning off the immune response. In past treatments for KS, drugs like M7824 achieved a response rate between 71% and 100%. This trial will also explore the combination of NHS-IL12 and M7824, which is expected to enhance the immune system's ability to combat KS tumors, based on these encouraging results. ^{1 3 4 6 7}

Who Is on the Research Team?

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04303117

NHS-IL12 Monotherapy and in Combination With M7824 in ... Anti-PD-L1 and anti-PD-1 agents have been found to be active in certain virus-induced cancers, including Kaposi sarcoma, and to be safe and active in patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11495121/

Classic Kaposi sarcoma: Diagnostics, treatment modalities ... The overall response rate in the treatment of classic KS was between 71% and 100% [47], with a time to treatment failure of 4 months and a duration of response ...

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04303117/

Clinical Trial: NCT04303117 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 ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2020-01754

NHS-IL12 Monotherapy and in Combination With M7824 ... 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 ...

5. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/view/40537/48021

Classic Kaposi sarcoma: Diagnostics, treatment modalities ... The overall response rate in the treatment of classic KS was between 71% and 100% [47], with a time to treatment failure of 4 months and a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9335510/

Preclinical and clinical studies of bintrafusp alfa, a novel ... Preclinical studies have demonstrated that bintrafusp alfa immune-mediating and antitumor activity can be enhanced by combining it with a human papillomavirus ( ...

7. medchemexpress.com medchemexpress.com/bintrafusp-alfa.html?srsltid=AfmBOoqpuULWJk1Jr5IRrdyKDBjHsmoZrWmd5Mrrmn0IHQwxdcvDdFQs

Bintrafusp alfa (M7824) | Bifunctional Fusion Protein Bintrafusp alfa can be used for the research of cancer. For research use only. We do not sell to patients.