Interleukin-2 + Pembrolizumab for Lung Cancer

Overseen By Suresh S. Ramalingam, MD, FACP, FASCO

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-PD-L1, others

Disqualifiers: Autoimmune disease, Transplant history, Active malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with stage IV non-small cell lung cancer (NSCLC) who have not yet tried other treatments for their advanced cancer. It investigates a combination of low-dose interleukin-2 (a protein that aids immune cells) and pembrolizumab (an immune therapy drug) to determine if it can enhance the body's ability to fight cancer. Individuals diagnosed with stage IV NSCLC and tumors expressing a protein called PD-L1 (which can help cancer cells evade the immune system) might be suitable candidates. The study aims to assess the effectiveness of this combination and its impact on the immune system. As an Early Phase 1 trial, this research focuses on understanding how the treatment functions in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take systemic immunosuppressive medications within 2 weeks before starting the trial, except for certain low-dose or inhaled medications.

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

Research shows that combining low-dose interleukin-2 (IL-2) with pembrolizumab is being tested to enhance the immune system's ability to fight cancer. Pembrolizumab has approval for several cancer types, indicating its general safety.

IL-2, used in higher doses for some cancers, can cause side effects like flu-like symptoms and low blood pressure. This study employs a lower dose of IL-2, expected to reduce side effects. Early-phase trials like this one primarily assess the treatment's safety for participants. The combination is still under careful study to ensure its safety.

The aim is to achieve a balance where the treatment is effective with manageable side effects. Prospective participants should stay informed and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of pembrolizumab and interleukin-2 (IL-2) for lung cancer because it offers a novel approach to enhancing the immune system's ability to fight cancer. Unlike standard treatments that often rely solely on chemotherapy or radiation, this combo leverages pembrolizumab, an immune checkpoint inhibitor, which helps unmask cancer cells to the immune system. Additionally, IL-2 acts as a powerful immune booster, potentially increasing the effectiveness of pembrolizumab by promoting the activity of immune cells. This dual-action strategy could offer a more robust and sustained attack on cancer cells, leading to better outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

In this trial, participants will receive a combination of interleukin-2 (IL-2) and pembrolizumab to evaluate its effectiveness in treating lung cancer. Research has shown that using a low dose of IL-2 with pembrolizumab might enhance the immune system's ability to fight lung cancer. Early studies indicate that pembrolizumab, a type of immune therapy, can help the body attack cancer cells in various cancers, including lung cancer. Adding IL-2 is believed to strengthen T cells, which play a crucial role in fighting cancer. Initial data suggest this combination can enhance T cell function, potentially improving outcomes for patients with stage IV non-small cell lung cancer (NSCLC). While more research is needed, these findings offer a hopeful basis for this treatment approach. ^{1 2 6 7 8}

Who Is on the Research Team?

Suresh S. Ramalingam

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with Stage IV non-small cell lung cancer (NSCLC) who haven't had prior treatments for advanced NSCLC can join. They need good organ function, measurable disease by RECIST criteria, life expectancy over 12 weeks, and some PD-L1 expression in tumors. Brain metastasis is okay if stable or symptom-free. Must not be pregnant and agree to use effective contraception.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I have Stage IV non-small cell lung cancer.

Patients must have a way to measure their disease that follows specific guidelines.

Exclusion Criteria

You have had serious allergic reactions to certain types of medications in the past.

I am currently being treated for another cancer.

Patients who are pregnant or lactating, or who are intending to become pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg IV every 3 weeks in combination with IL-2 given at 5 million IU subcutaneously twice daily for 3 weeks

3 weeks

First dose in clinic, subsequent doses at home

Monotherapy

Pembrolizumab is continued as monotherapy at either 200 mg every 3 weeks or 400 mg every 6 weeks

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Pembrolizumab

Trial Overview

The trial tests a combination of low-dose interleukin-2 (IL-2) and pembrolizumab on patients with untreated stage IV NSCLC. It aims to see if this combo reactivates T cells against the tumor better than previous methods, checking both immune response and clinical outcomes.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, aldesleukin) Experimental Treatment 2 Interventions

Patients will be treated with pembrolizumab 200 mg IV once every 3 weeks in combination with IL-2 given at 5 million IU subcutaneously twice daily for 3 weeks (5 days on, 2 days off each week, first dose in clinic and subsequent doses at home). IL-2 will be given only for the three weeks, after which pembrolizumab will be continued as monotherapy at either 200 mg every 3 weeks or 400 mg every 6 weeks.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

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) 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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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, 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]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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, 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, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05493566

Study Details | NCT05493566 | Low-Dose Interleukin-2 ...

This early phase 1 trial will investigate the combination of low-dose interleukin-2 (IL-2) and pembrolizumab in patients with previously untreated stage IV ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11804207/

Pembrolizumab hybrid dosing is non-inferior to flat ...

This study provides important evidence in a large cohort of patients with advanced NSCLC that pembrolizumab dosing can be optimized by lowering ...

3.

aacrjournals.org

aacrjournals.org/clincancerres/article/21/19/4286/125563/Phase-I-Study-of-Pembrolizumab-MK-3475-Anti-PD-1

Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 ...

Although not powered for efficacy, pembrolizumab demonstrated evidence of antitumor activity in multiple tumor types, including melanoma, NSCLC, and Merkel cell ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1558767322000234

Coordinated Pembrolizumab and High Dose IL-2 (5-in-a- ...

Single agent objective response rates of 14% to 25% have been reported for usual schedule 14-dose-in-a-row IL-2 therapy of metastatic clear cell renal cancer ( ...

5.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-00931

Low-Dose Interleukin-2 and Pembrolizumab for the ...

Giving IL-2 and pembrolizumab may improve the response of the immune system against cancer and result in better outcomes in patients with stage IV non-small ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4918260/

Update on use of aldesleukin for treatment of high-risk ...

In this article, we review preclinical and clinical data regarding interleukin-2, its pharmacology and mechanism of action, its toxicity profile, and its use in ...

7.

cancer.gov

cancer.gov/research/participate/clinical-trials/intervention/aldesleukin?pn=1

Clinical Trials Using Aldesleukin - NCI

Clinical Trials Using Aldesleukin. Review the clinical trials studying aldesleukin on this list and use the filters to refine the results by age and location.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4315731/

The High-Dose Aldesleukin “Select” Trial - PubMed Central

High-dose aldesleukin (HD IL-2) received FDA approval for the treatment of mRCC in 1992, producing a 14% objective response rate (ORR) and durable ...