Pembrolizumab + Interleukin-12 for Cancer

Recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two treatments for patients with solid tumors. One treatment helps the immune system attack cancer, and the other cuts off the tumor's blood supply and boosts the immune response. The goal is to find the best dose and see if this combination works effectively. Combining targeted and immunotherapy is a rapidly growing practice in solid tumors and provides a glimpse of hope in situations that previously lacked any treatment option.

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.

What data supports the effectiveness of the drug Pembrolizumab + Interleukin-12 for cancer?

While there is no direct data on Pembrolizumab + Interleukin-12 for cancer, similar treatments like ustekinumab, which targets interleukin-12, have shown effectiveness in conditions like psoriatic arthritis and Crohn's disease, suggesting potential benefits in modulating immune responses. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Interleukin-12 safe for humans?

Pembrolizumab, also known as Keytruda, has been studied for safety in humans and is generally considered safe, but it can cause some immune-related side effects like type 1 diabetes in rare cases and pneumonitis (lung inflammation) in 1%-5% of patients. In nonhuman primate studies, no significant toxic effects were observed. However, specific safety data for the combination with Interleukin-12 is not provided in the available research. ^{6 7 8 9 10}

What makes the drug Pembrolizumab + Interleukin-12 unique for cancer treatment?

This treatment combines Pembrolizumab, a drug that helps the immune system attack cancer by blocking a pathway that tumors use to hide, with Interleukin-12, which boosts the immune response. This combination aims to enhance the body's ability to fight cancer more effectively than using either component alone. ^{6 7 10 11 12}

Research Team

Diwakar Davar, MD

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Eligibility Criteria

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

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

Known allergic reactions to study compounds

I do not have any unmanaged ongoing illnesses.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis. [2022]

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

Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Remission, low disease activity and improvement of pain and function in psoriatic arthritis patients treated with IL-12/23 and IL-17 inhibitors. A multicenter prospective study. [2021]

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

Ustekinumab Is Associated with Real-World Long-Term Effectiveness and Improved Health-Related Quality of Life in Crohn's Disease. [2023]

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

Ustekinumab for the treatment of Crohn's disease. [2017]

6. United States 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. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

11. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

12. England pubmed.ncbi.nlm.nih.gov

First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma. [2023]