Pembrolizumab + Interleukin-12 for Cancer

Not currently recruiting at 33 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Hematological malignancy, Autoimmune cytopenias, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 8 cycles of 28 days for cycle 1 and 21 days for subsequent cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pembrolizumab and interleukin-12 (also known as edodekin alfa), to evaluate their effectiveness against solid tumors. Pembrolizumab, a type of immunotherapy, helps the immune system attack cancer, while interleukin-12 blocks blood flow to tumors and boosts white blood cells to kill cancer cells. The trial aims to determine the best dose and understand the side effects when these treatments are combined. It may suit individuals with advanced solid tumors that cannot be surgically removed and who have not responded to similar therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or immunosuppressive therapy within 7 days before the trial starts. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that pembrolizumab, a type of immunotherapy, is generally safe for patients. In one study with 8,937 participants, many received the treatment multiple times, with some receiving up to 59 doses, indicating a strong safety record.

Recombinant interleukin-12, another component of this trial's treatment, has shown promise in cancer therapy. It boosts the immune system and reduces blood flow to tumors. Some studies reported no serious side effects, allowing patients to continue treatment without stopping due to negative reactions.

Overall, both pembrolizumab and recombinant interleukin-12 have demonstrated encouraging safety results in previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Interleukin-12 for cancer treatment because it offers a unique approach compared to current therapies. Pembrolizumab, an immune checkpoint inhibitor, works by unleashing the immune system to attack cancer cells, while Interleukin-12 boosts the immune response even further. This dual-action strategy aims to enhance the body's natural defenses against cancer more effectively than using Pembrolizumab alone. By combining these two treatments, there's potential for improved outcomes and possibly faster responses in patients who might not respond to standard therapies.

What evidence suggests that pembrolizumab and recombinant interleukin-12 might be an effective treatment for solid tumors?

In this trial, participants will receive a combination of pembrolizumab and interleukin-12. Research has shown that pembrolizumab, a treatment that aids the immune system in fighting cancer, shows promise in treating various cancers. Studies have found that some patients using pembrolizumab achieve a five-year survival rate of up to 22%, surpassing traditional chemotherapy outcomes. Interleukin-12, also known as edodekin alfa, can enhance the immune system's ability to combat cancer by potentially stopping tumors from growing through the reduction of their blood supply. When used together in this trial, pembrolizumab and interleukin-12 might prove more effective than pembrolizumab alone, possibly leading to better outcomes for patients with solid tumors. ^{2 3 5 6 7}

Who Is on the Research Team?

Diwakar Davar, MD

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that have worsened after anti-PD-(L)1 therapy. They must be in good physical condition, not pregnant or breastfeeding, and willing to use birth control. People can't join if they've had recent cancer treatments, other active cancers, immune system problems, untreated brain metastases, severe allergies to study drugs, or are on steroids.

Inclusion Criteria

My liver and kidney tests are normal.

My cancer has not responded to previous anti-PD-(L)1 therapy.

I am mostly active and can care for myself.

Exclusion Criteria

Known allergic reactions to study compounds

I have an immune system disorder or have recently been on steroids.

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive recombinant interleukin-12 subcutaneously and pembrolizumab intravenously over multiple cycles

Up to 8 cycles of 28 days for cycle 1 and 21 days for subsequent cycles

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks for 2 years, then every 24 weeks for up to 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Edodekin alfa
• Pembrolizumab

Trial Overview The trial tests pembrolizumab (an antibody that helps the immune system fight cancer) combined with recombinant interleukin-12 (which may block tumor blood flow and activate white cells against the tumor). It aims to find a safe dose and see if this combo is more effective than pembrolizumab alone.

How Is the Trial Designed?

Group I: Treatment (recombinant interleukin-12, pembrolizumab) Experimental Treatment 7 Interventions

Patients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, PET, and MRI, as well as collection of blood during screening, on study, and during follow-up. Patients also undergo a tumor biopsy during screening and on study.

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

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Ustekinumab is an effective treatment for moderate-to-severe ulcerative colitis (UC), targeting the IL-12 and IL-23 pathways, and has a favorable safety profile with low immunogenicity, making it a good option after other treatments have failed.

Current studies suggest that ustekinumab can be used safely as monotherapy for UC, but more research is needed to clarify its optimal use and effectiveness in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis. Miyoshi, J., Matsuura, M., Hisamatsu, T.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11098992/

Interleukin-12 in multimodal tumor therapies for induction ... Interleukin-12 (IL-12) can be used as an immunomodulator in cancer immunotherapy. And it has demonstrated enormous potential in inhibiting tumor growth.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03030378?term=INTERLEUKIN-12%20HUMAN%20RECOMBINANT&viewType=Table&rank=6

Pembrolizumab and Recombinant Interleukin-12 in ... Giving pembrolizumab and recombinant interleukin-12 may work better than giving pembrolizumab alone in treating patients with solid tumors.

3. synapse.patsnap.com synapse.patsnap.com/drug/4ea798a3fe3047d08810e48f7625e4d9

Edodekin alfa - Drug Targets, Indications, Patents Strikingly, oHSV-IL12 monotherapy achieved complete tumor eradication, surpassing the efficacy of oHSV-GMCSF. RNA sequencing analysis revealed that oHSV-IL12 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41022754/

Interleukin-12 anchored drug conjugate (tolododekin alfa) ... At a median follow-up of 5.2 months, the median duration of stable disease was 5.3 months (range 3.6-7.6 months). Median progression-free ...

5. researchgate.net researchgate.net/publication/380636569_Interleukin-12_in_multimodal_tumor_therapies_for_induction_of_anti-tumor_immunity

(PDF) Interleukin-12 in multimodal tumor therapies for ... Interleukin-12 (IL-12) can be used as an immunomodulator in cancer immunotherapy. And it has demonstrated enormous potential in inhibiting tumor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03030378

Pembrolizumab and Recombinant Interleukin-12 in ... Recombinant interleukin-12 may kill tumor cells by blocking blood flow to the tumor and by stimulating white blood cells to kill tumor cells.

7. xiliotx.com xiliotx.com/pipeline/efarindodekin-alfa-xtx301

Efarindodekin Alfa (XTX301) Efarindodekin alfa (XTX301) is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram ...