What side effects are associated with this type of intervention?

Common treatments for solid tumors, such as pembrolizumab (a monoclonal antibody immunotherapy) and recombinant interleukin-12 (a cytokine therapy), have distinct side effect profiles. Pembrolizumab can cause fatigue, rash, diarrhea, and severe immune-mediated effects like pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Recombinant interleukin-12 may lead to flu-like symptoms, fatigue, fever, chills, nausea, and severe effects like hypotension and liver toxicity. Combining these therapies may enhance the immune response but also increase the risk of compounded side effects.

What prior FDA approvals exist?

Pembrolizumab, an anti-PD-1 monoclonal antibody, has received FDA approval for various solid tumors, including melanoma, non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma, among others. Other similar immunotherapies include nivolumab, another anti-PD-1 antibody, approved for melanoma, NSCLC, and renal cell carcinoma, and atezolizumab, an anti-PD-L1 antibody, approved for NSCLC and urothelial carcinoma. While recombinant interleukin-12 itself is not widely approved, cytokine therapies like high-dose interleukin-2 have been approved for metastatic renal cell carcinoma and metastatic melanoma.

What other types of research exist?

Promising novel alternatives for solid tumor treatment in 2024 include: <ol> <li>Cemiplimab: A PD-1 inhibitor that has shown efficacy in combination with chemotherapy for non-small cell lung cancer.</li> <li></li> </ol> Nivolumab plus Ipilimumab: This combination has demonstrated long-term benefits in various cancers, including non-small cell lung cancer and melanoma. 3. Avelumab: A PD-L1 inhibitor that has shown durable responses in mesothelioma and other solid tumors. 4. TrisomAb: An augmented antibody-based therapeutic that boosts neutrophil cytotoxicity, potentially offering benefits for patients not responding to current IgG mAb therapies.

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Cytokine

Pembrolizumab + Interleukin-12 for Cancer

Phase 1

Waitlist Available

Led By Diwakar Davar

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have tumors with an FDA-approved indication for anti-PD-(L)1 therapy and have progressed past anti-PD(L)1 therapy

Age >= 18 years

Must not have

Diagnosis of immunodeficiency or recent systemic steroid therapy

Uncontrolled intercurrent illnesses

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal organs (autoimmunity), infusion-related reactions from receiving the drug into a vein, fatigue, changes in blood counts which could increase infection risk or cause bleeding issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I am mostly active and can care for myself.

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My cancer has spread and cannot be removed with surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I do not have any unmanaged ongoing illnesses.

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I have had a condition where my lymphocytes grow abnormally.

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I have a history of autoimmune blood disorders.

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I have a secondary blood cancer.

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I have not received a live vaccine recently.

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I have active brain tumors or cancer that has spread to my brain.

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I am on medication for an autoimmune disease.

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I have recently been on corticosteroid medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

CD8+ T cell infiltration

Incidence of adverse events

Overall response rate

+1 more

Other study objectives

Biomarker analysis

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (recombinant interleukin-12, pembrolizumab)Experimental Treatment7 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Positron Emission Tomography

2011

Completed Phase 2

~2200

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Biopsy

2014

Completed Phase 4

~1150

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Monoclonal antibody immunotherapy, such as pembrolizumab, targets specific proteins like PD-1 on cancer cells to block inhibitory signals and enhance the immune system's ability to attack the tumor. Cytokine therapy, such as recombinant interleukin-12, boosts the immune response by stimulating white blood cells and inhibiting blood flow to the tumor. These targeted approaches are crucial for solid tumor patients as they enhance the body's natural defenses against cancer, potentially leading to better outcomes and fewer side effects compared to traditional therapies.