29 Participants Needed

IL2 + Ipilimumab and Nivolumab for Melanoma

LM
LT
Overseen ByLeticia Tetth
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must not have had systemic therapy or radiotherapy within 3 weeks before joining. If you are on steroids, you need to stop them at least 2 weeks before starting the trial.

What data supports the effectiveness of the drug combination IL2, Ipilimumab, and Nivolumab for treating melanoma?

Research shows that IL-2 can induce durable responses in some melanoma patients, and the combination of Ipilimumab and Nivolumab has been effective in improving survival in advanced melanoma. Additionally, adding IL-2 to Ipilimumab and Nivolumab has shown promise in overcoming resistance in some cancer treatments, suggesting potential benefits for melanoma.12345

What safety data exists for the combination of IL2, Ipilimumab, and Nivolumab in humans?

Nivolumab and Ipilimumab, used to treat various cancers, can cause immune-related side effects, including colitis (inflammation of the colon). These side effects are known as immune-related adverse events (irAEs) and can sometimes be managed with other medications like infliximab.678910

What makes the IL2 + Ipilimumab and Nivolumab treatment unique for melanoma?

This treatment combines three drugs that work together to boost the immune system's ability to fight melanoma. Interleukin-2 (IL-2) helps grow immune cells, while Ipilimumab and Nivolumab block proteins that stop the immune system from attacking cancer cells, making this combination a novel approach compared to using each drug alone.111121314

Research Team

Ahmad Tarhini | Moffitt

Ahmad Tarhini, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with advanced melanoma who have had prior anti-PD1 immunotherapy but their disease got worse. They must be in good health otherwise, not have serious heart issues or brain metastasis, and agree to use contraception. It's not for those with autoimmune diseases on steroids, other cancers (unless free of disease for over 2 years), or recent treatments that they haven't recovered from.

Inclusion Criteria

I haven't had a stroke or mini-stroke in the last 6 months.
I am over 50 or have a history of lung issues or smoking, and need lung function tests.
I had major surgery over 4 weeks ago and have fully recovered.
See 10 more

Exclusion Criteria

I do not have serious heart or brain blood vessel problems.
Receiving any other investigational agents
I have active cancer spread to my brain.
See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose bolus IL2 in combination with low dose ipilimumab followed by nivolumab for up to 3 courses

12 weeks per course (up to 3 courses)
Multiple visits per cycle

Response Assessment

Response assessment occurs at the end of the 4th cycle of each course

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

  • Interleukin-2
  • Ipilimumab
  • Nivolumab
Trial OverviewThe study tests if giving Interleukin-2 at the same time as ipilimumab followed by nivolumab can better fight advanced melanoma. Participants will receive these drugs sequentially to see if this combination improves cancer control compared to previous treatments they've received.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment3 Interventions
HD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg during week one of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on during week one of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.

Interleukin-2 is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Aldesleukin for:
  • Metastatic melanoma
  • Metastatic renal cell carcinoma
🇪🇺
Approved in European Union as PROLEUKIN for:
  • Metastatic renal cell carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials
576
Recruited
145,000+

Clinigen, Inc.

Industry Sponsor

Trials
10
Recruited
360+

Findings from Research

A patient with metastatic renal cell carcinoma showed no tumor regression with PD-1 blockade but achieved a near-complete response after receiving high-dose IL-2 therapy, highlighting IL-2's potential as an effective second-line treatment.
This case underscores the importance of developing better predictors for response to immunotherapies, which could help optimize treatment sequences and determine when to switch to alternative therapies.
Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment.Brayer, J., Fishman, M.[2020]
High-dose Interleukin-2 (HDIL2) is FDA-approved for treating metastatic melanoma and renal cell carcinoma, showing durable responses in 5-10% of patients by enhancing T cell activity and altering the tumor microenvironment.
The use of HDIL2 can lead to autoimmunity in some patients, indicating that while it can effectively promote antitumor responses, it may also disrupt immune tolerance, necessitating further investigation into its mechanisms of action.
Focus on FOCIS: interleukin 2 treatment associated autoimmunity.Moschos, SJ., Mandic, M., Kirkwood, JM., et al.[2021]
In metastatic melanoma patients, treatment with the immune checkpoint inhibitor Nivolumab altered the proportions and functions of innate lymphoid cells (ILCs), leading to increased secretion of important cytokines like IL-13 and TNFα.
Higher levels of CCL2 before treatment were linked to better survival outcomes, while after two months of Nivolumab therapy, certain ILC subpopulations and serum cytokine levels negatively correlated with overall survival and progression-free survival, indicating their potential role in therapy response.
Altered Frequencies and Functions of Innate Lymphoid Cells in Melanoma Patients Are Modulated by Immune Checkpoints Inhibitors.Cristiani, CM., Capone, M., Garofalo, C., et al.[2022]

References

Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment. [2020]
Focus on FOCIS: interleukin 2 treatment associated autoimmunity. [2021]
Altered Frequencies and Functions of Innate Lymphoid Cells in Melanoma Patients Are Modulated by Immune Checkpoints Inhibitors. [2022]
[Immune checkpoint inhibitors for treatment of advanced stage melanoma]. [2020]
Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors. [2022]
Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. [2020]
Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial. [2022]
Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. [2022]
Impact of Selective Immunosuppressive Therapy on Subsequent Immune-Related Adverse Events After Immune Checkpoint Inhibitor-Induced Colitis Treatment. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin 2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma. [2023]
Nivolumab: a review of its use in patients with malignant melanoma. [2021]
13.United Statespubmed.ncbi.nlm.nih.gov
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. [2023]
14.United Statespubmed.ncbi.nlm.nih.gov
Neoadjuvant Pembrolizumab and High-Dose IFNα-2b in Resectable Regionally Advanced Melanoma. [2023]