6 Participants Needed

IL-2 + Nivolumab for Melanoma

MK
GD
Overseen ByGregory Daniels, MD, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Gregory Daniels
Must be taking: Anti-PD-1 therapy
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

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on high-dose systemic steroids or immunosuppressive medications, and you must not have taken any investigational agents within 21 days before starting the trial. Please discuss your specific medications with the trial team.

What data supports the idea that IL-2 + Nivolumab for Melanoma is an effective treatment?

The available research shows that combining IL-2 with Nivolumab can be effective for treating melanoma. In particular, a study found that adding bempegaldesleukin (a form of IL-2) to Nivolumab improved responses in patients with metastatic melanoma, with 20 out of 38 patients showing positive results. This combination was also well-tolerated, meaning it didn't cause many side effects. Additionally, another study compared this combination to Nivolumab alone and found it to be more effective in preventing the return of melanoma after surgery. These findings suggest that IL-2 combined with Nivolumab can be a promising treatment option for melanoma.12345

What safety data exists for IL-2 and Nivolumab treatment in melanoma?

Safety data for IL-2 (Aldesleukin) and Nivolumab (Opdivo) in melanoma includes reports of immune-related adverse events (irAEs) such as pneumonitis, hypothyroidism, dermatitis, enterocolitis, hepatitis, and neuropathy associated with Nivolumab. IL-2 has been associated with severe adverse events, particularly with the original intravenous bolus regimen, which often requires intensive care. However, continuous intravenous infusion and subcutaneous administration have reduced the severity of these adverse events. The combination of Bempegaldesleukin (a modified IL-2) and Nivolumab was well-tolerated in early trials, with further safety assessments ongoing in a Phase III trial. Overall, while both treatments have shown efficacy, their risk/benefit profiles require careful consideration due to potential toxicities.12678

Is the drug IL-2 and Nivolumab a promising treatment for melanoma?

Yes, IL-2 and Nivolumab show promise as a treatment for melanoma. IL-2 can lead to long-lasting responses in melanoma patients by boosting the immune system. Nivolumab, which helps the immune system attack cancer cells, has been shown to improve survival in advanced melanoma. Together, they have demonstrated clinical activity and potential for effective treatment.135910

What is the purpose of this trial?

The primary objective of this single arm phase 2 trial is to assess the response rate \[complete response (CR) + partial response (PR)\] of combined nivolumab and HD IL-2 in subjects with metastatic melanoma and renal cell carcinoma. Response will be performed after each course of nivolumab and IL-2 using RECIST 1.1. Patients will be treated for one course past best response for a maximum of 3 courses.

Eligibility Criteria

Adults with metastatic melanoma or renal cell carcinoma who've previously tried anti-PD-1 therapy without success. They must be in good physical condition, not pregnant, willing to use birth control, and have recovered from previous treatments' side effects. Exclusions include active infections, other recent cancers (except certain localized ones), uncontrolled hypertension, mental conditions preventing consent, and certain medical histories like autoimmune diseases.

Inclusion Criteria

I've had anti-PD-1 therapy for over 6 weeks and my cancer progressed after.
I am fully active or restricted in physically strenuous activity but can do light work.
I am not pregnant and agree to use two forms of birth control.
See 10 more

Exclusion Criteria

I am mentally and physically capable of participating in a clinical trial.
I am taking more than 10 mg of prednisone daily.
I haven't had a heart attack or stroke in the last 6 months.
See 12 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined therapy with nivolumab and high dose IL-2 for up to 3 courses, with response assessments after each course

Up to 3 courses
Visits prior to each treatment and after each course

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment

1 year +/- 3 months

Treatment Details

Interventions

  • IL-2
  • Nivolumab
Trial Overview The trial is testing the combination of nivolumab (an anti-PD-1 drug) and high-dose IL-2 to see if they can work together to treat patients whose cancer didn't respond to just anti-PD-1 treatment alone. Patients will receive these drugs for up to three courses and their response will be measured using standard criteria.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: High Dose IL-2 and NivolumabExperimental Treatment1 Intervention

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

🇺🇸
Approved in United States as Proleukin for:
  • Renal cell carcinoma
  • Melanoma
🇪🇺
Approved in European Union as Proleukin for:
  • Renal cell carcinoma
  • Melanoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Gregory Daniels

Lead Sponsor

Trials
2
Recruited
30+

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]
The combination of bempegaldesleukin (BEMPEG) and nivolumab has shown promising clinical activity and good tolerability as a first-line treatment for metastatic melanoma in the Phase I/II PIVOT-02 trial.
The ongoing Phase III PIVOT IO 001 trial aims to compare the effectiveness of this combination therapy against nivolumab alone, focusing on key outcomes like objective response rate and overall survival in patients with untreated metastatic melanoma.
Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design.Khushalani, NI., Diab, A., Ascierto, PA., et al.[2021]
In a phase 2 trial involving 89 patients with advanced melanoma, the combination of ziv-aflibercept and IL-2 significantly improved progression-free survival (PFS) to a median of 6.9 months compared to 2.3 months for IL-2 alone (P<.001).
The combination therapy showed similar overall survival rates between the two groups, indicating that while PFS improved, the overall survival benefit may need further investigation.
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.Tarhini, AA., Frankel, P., Ruel, C., et al.[2023]

References

Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment. [2020]
Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. [2021]
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]
Bempegaldesleukin Ups Melanoma Responses. [2020]
PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence. [2022]
Aldesleukin (recombinant interleukin-2). [2022]
Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. [2021]
Febrile Neutropenia in a Patient with Non-Small Cell Lung Cancer Treated with the Immune-Checkpoint Inhibitor Nivolumab. [2020]
Multifunctionality of CD8+ T cells and PD-L1 expression as a biomarker of anti-PD-1 antibody efficacy in advanced melanoma. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. [2022]
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